From the early IV century AD, the eastern regions of Sasanian Iran, commonly referred to as Bactria-Tokharistan, were invaded by various hostile peoples. For that reason, the struggle against eastern foes became one of the most important vectors of Shapur II’s (309–379) foreign policy. An analysis of the primary sources shows that Shapur’s eastern campaigns were the result not so much of his pursuit of military expansion as that of the ethnopolitical processes in Bactria-Tokharistan and adjacent regions in the IV century AD. In this regard, the wars waged by Shapur II on the Iranian eastern frontiers were defensive rather than offensive in nature and could be divided into three steps. At the first stage (late 320’s – mid-330’s AD), they were caused by the necessity to put an end to the strengthening of Kushanshahr, which has evolved from a vassal principality to an independent state, pursuing a hostile policy towards Sasanian Iran. The second eastern campaign of Shapur II (350’s AD) was triggered by the invasion of Bactria-Tokharistan by nomadic tribes known as the Chionites, who not only occupied the territory of Kushanshahr but also claimed the eastern regions of Sasanian kingdom. The final phase of Shapur II’s wars in Eastern Iran (370’s AD) represented a military conflict with the Kidarites’ who, obviously, were the dynasty of Chionite origin too, but managed to establish their own realm on the territory of former Kushanshahr and some neighbor areas. The immediate result of all these events consisted in the loss of control over Bactria-Tokharistan by the Persians. In the longer-term, the Sasanids were forced for several decades (until the reign of Yazdegerd II) to give up the attempts to return this region into the sphere of their political influence.