SASSANIAN PERIOD Ardashir's power was rising when the Parthian Artabanus died in 224 (227) , and Ardashir proposed to prove himself the suc cessor of the Achaemenidae. Hatra resisted the first Persian at tack as it had resisted Rome ; but Mesopotamia was overrun, Nisibis and Carrhae being taken (233). It was immediately, in deed, recovered by Alexander Severus, and retained, whatever was the precise success of the war; but Nisibis and Carrhae were retaken by the Persians in the reign of Maximin. Under Gordian III. in 242 Mesopotamia was entered by a great Roman army which recovered Carrhae and Nisibis, and defeated the Persians at Resaena ; but when Gordian after a difficult march down the Kha.bur, was murdered at Zaitha below Circesium, Philip the Arabian (244) made the best terms he could with Shapur I. Whatever they were, the Roman garrisons seem not to have been really withdrawn. A rest for Mesopotamia seems to have fol lowed; but in 258 Shapur, tempted by the troubles in the Roman empire, overran the country taking Nisibis and Carrhae, and in vesting Edessa, and when Valerian invaded Mesopotamia he was eventually made prisoner near Edessa (26o). After Shapur's cruel victories in Syria, however, he was defeated by Odaenathus, who relieved Edessa, and Mesopotamia became for ten years practically part of an Arabian empire (see PALMYRA), as it was to be four centuries later. In consequence of the revolt of Zeno bia. Mesopotamia was lost to Rome, and the Euphrates became the frontier. Aurelian overthrew the Palmyran rule ; but he was assassinated before he could carry out his intended expedition against Persia, Probus was assassinated before he was able to do anything (or much), and although Carus easily overran Mesopo tamia, which became Roman again, and even took Ctesiphon, the Romans retreated on his death (283-284). The next incident is the defeat of Galerius, between Carrhae and Callinicus, where he had entered Mesopotamia (about 296), in the war provoked by Narses in consequence of his relations with Armenia. When it was retrieved by a signal victory, Diocletian advanced to Nisibis and thence dictated terms of peace by which Mesopotamia to the Tigris was definitely ceded to Rome (298).
After a forty years' peace the struggle was resumed by Shapur II. Nisibis thrice endured unsuccessful siege (338, 346, although meanwhile Constantine had suffered defeat at Singara (348). Then Mesopotamia enjoyed two short rests (separated by a sharp struggle) while the rivals were engaged elsewhere, when in 363 Julian (q.v.) made his disastrous attempt, and Jovian bought peace at the price, among other things, of Singara and Nisibis, i.e., practically all eastern Mesopotamia.
The surrender of Nisibis, which had been in the possession of Rome for so many generations, caused consternation among the Christians, and Ephraem (q.v.) moved to Edessa, where his "school of the Persians" soon became famous (see EDESSA). In the war of 421, in which the north-east of Mesopotamia was chiefly concerned, the Romans failed to take Nisibis, and it be came a natural rallying point for the Nestorians after the decision of Ephesus (431). Matters were still more complicated when the Western Christians of Edessa found themselves unable to accept the ruling of Chalcedon against Monophysitism in 451 (see MONO PHYSITES), and there came to be three parties : Nestorians (q.v.), Jacobites (see JACOBITE CHURCH) and Melchites (q.v.).
In the beginning of the 6th century there was another severe struggle in Mesopotamia, which found an anonymous Syriac his torian (see EDESSA), and in infringement of agreement the Ro mans strongly fortified Dara against Nisibis. The Persian inva sion of Syria under Kavadh I. (q.v.) was driven back by Beli sarius; but the latter was defeated in his pursuit at Rakka (531). The peace begun by Chosroes I. (532) was not long kept, and Ro man Mesopotamia, except the pagan ljarran, suffered severely (54o), Edessa undergoing a trying siege (544). The fifty years' peace also (562) was short lived; the Romans again failed in an attempt to recover Nisibis (573), whilst Chosroes' siege of Dara was successful. Mesopotamia naturally suffered during the time of confusion that preceded and followed the accession of Chosroes II., and the Romans recovered their old frontier (591).