Rome's powerful eastern neighbors were the Parthians. In 53 BC, the Parthians had defeated Crassus (a Roman general) at Carrhae. This conquest gave the Parthians a distinct advantage in the ongoing struggle between themselves and the Romans. The Parthias had also severely damaged Mark Antony's army in 36 BC. However, they were very much weakened by the time the second century BC rolled around. Trajan took control of Mesopotamis from the Parthians in 114 AD He then lost control, but fifty years later, the Romans (under Marcus Aurelius and Lucius Verus, then ruling jointly) invaded again, sacking Ctesiphon (the Parthian capital of Mesoptamia). Parthia had been weakened by internal conflicts, and this contributed to the ease with which it was conquered. The Parthians supported Pescennius Niger, who was the sworn enemy of Septimius Severus. To punish them for this, Severus captured Nisibis and established the Roman province of Osrhoene. Then Ctesiphon was sacked again, and finally Severus formed the Roman province of Mesopotamia.
The main goal for Severus's son Caracalla was a further invasion of Parthia. In 216 AD, he began his attack, invading Arbela in Media, beyond the River Tigris. Again, Parthia had been weakened by internal struggles for the throne. In 217 AD, though, they forced the Romans to come to terms. Caracalla had been murdered on the way from Edessa to Carrhae.