Emperor Valerian, who has taken charge of the empire's eastern frontiers, rushes to the aid of Doura-Europus, but he cannot remedy the situation.

The city, destroyed in the Persian siege, is abandoned completely.

Later in 259, ...

...the emperor moves to Edessa, but an outbreak of plague kills a critical number of legionaries, weakening the Roman position.

Shapur battles the Roman forces under to a standstill, encircling his army.

Desperate, the sixty-six-year-old emperor enters into peace negotiations with Shapur, during operations about which little is known.

Valerian’s son and co-emperor Gallienus fights a series of campaigns against the Goths on the Upper Rhine.

While Valerian is fighting against the Sassanid Empire and the Goths, who by this time have sacked Thrace and Asia Minor, Gallienus will be in charge of defending the Roman Empire's border.

In the Western half of the Empire, the situation is difficult.

The Danubian border resists continuous barbarian attacks.

Gallienus has to march with military reinforcements from Gaul towards Dacia and Moesia to fight the barbarians.

The situation is so severe that in 259, the legions of Pannonia and Moesia rebel and choose to make Ingenuus the emperor.

Gallienus reunites the Rhine, leaves a Roman legion their to defend it and goes off to do battle.

Within the borders of the Rhine and the Alps, a Germanic confederation, the Alamanni, who occupy a good part of the Agri Decumates (a region of the Roman Empire's provinces of Germania Superior and Raetia, covering the Black Forest, Swabian Jura, and Franconian Jura areas between the Rhine, Main, and Danube rivers), cross the Alps and attack the fertile plain of the Po river.

The sacking of the area instills terror in Rome, as the city remains unwalled.

The Senate of Rome hastily prepares a crowd of plebs for combat in an attempt to ensure that its shrinking army is capable of protecting the city.

Gallienus had just defeated the pretender Ingenuus when the news arrives of the invasion by the Alamanni.

He marches off with three legions to intercept the barbarians in Italy.

By then, according to the Byzantine historian Joannes Zonaras, the Alamanni had retreated before the unexpected resistance of the citizens of Rome and its Senate.

When Gallienus arrives in the valley of the Po, he finds the Alamanni in the vicinity of Mediolanum, present day Milan.

The victory is total: according to Zonaras three hundred thousand Alamanni fell that day and the emperor received the title Germanicus Maximus.

The Alamanni's success in reaching into the Roman Empire once more reveals the weakness of the centuries-old tradition of posting Rome's legions near the borders without providing for defense within the empire.

The battle of Mediolanum demonstrates to the Romans the value of swift, flexible military units.

Afterward, Gallienus enacts a major reform by introducing a highly mobile field army composed mainly of cavalry (vexillationes).

The main units are under the control of his general, Aureolus, and headquartered in Mediolanum, with the mission to protect Italy.

Finally, the invasion by the Alamanni demonstrates the vulnerability of Italy and especially Rome.

This later causes Emperor Aurelian to have a strong wall built to defend the capital of the Empire.

The Juthungi, an Alemannic tribe in the region north of the rivers Danube and Altmühl in the modern German state of Bavaria, invade Italy in the winter of 259–260, but on their way back they are defeated near Augsburg on April 24–25, 260 by Marcus Simplicinius Genialis (this is recorded on a Roman memorial stone found in 1992).

At this time the Roman Empire loses the Limes area in this region.

The Pannonias, with Valerian’s capture in the East, fall under grave threat from the Germanic tribes, and Regalianus, one of the usurpers proclaimed by the Pannonian legions, dies fighting the invaders.

The defense is concentrated around Sirmium and ...

...Siscia, the ancient fortresses that had been restored by Gallienus; many cities are burned.

Palmyra, ('city of palm trees'), a long-prominent trading city built on an oasis along one of the main routes of east-west trade one hundred and forty miles (two hundred and thirty kilometers) northeast of Damascus, had come under Roman control by the time of the emperor Tiberius.

However, with the Sassanians having supplanted the Parthians in Persia and southern Mesopotamia in 227, the road to the Persian Gulf had soon been closed to Palmyrene trade.

Still relatively autonomous, Palmyra has grown increasingly wealthy and influential due to its tariff on the caravans passing through the city.

In return, the local rulers have policed caravan routes and the border area.

Instability around the Roman-controlled Mediterranean, coupled with the interruption of caravan trade with the East, had led the Romans to set up the personal rule here of the leading Palmyrene family of Septimius Odainath, or Odaenathus, a Roman citizen appointed governor of Syria Phoenice by Valerian.

The year is not known, but already in an inscription dated 258 he is styled "the illustrious consul our lord".

The defeat and captivity of Valerian in 260 has left the eastern provinces largely at the mercy of the Persians; the prospect of Persian supremacy is one that neither Palmyra nor its ruler have any reason to desire.

At first, it seems, Odaenathus had attempted to propitiate the Persian monarch Shapur.

However, when his gifts had been contemptuously rejected (Petr. Patricius, 10) he had decided to throw in his lot with the cause of Rome to prevent his city from falling under Sassanian control.

He thus abandons the neutrality that has made Palmyra's fortune for an active military policy that, while it will add to Odaenathus's fame, in a short time will bring his native city to its ruin.

Before Shapur’s army, returning home in 260 rich in plunder from its sack of Antioch, can cross the Euphrates, Odaenathus deals it a severe defeat, thereby curtailing further Persian aggression in Syria and Asia Minor.

All the stone carvings on Naqsh-e Rustam, in Iran, depict Valerian respectfully as holding hands with Shapur as a sign of his submission.

Shapur uses the remaining captured Roman soldiers in civil engineering and development plans.

Band-e Kaisar (Caesar's dam) is one of the remnants of Roman engineering located near the ancient city of Susa.

The Persians, who have devastated the East just as the Germanic tribes had recently plundered the Rhine and Danube provinces, plunder Cappadocia, ...