Abstract: The article analyzes the main factors influencing the formation of Iran's foreign policy in the Middle East in the context of solving the problem of settlement of the Iran’s nuclear program and application of the sanctions regime. A special attention is given to consideration of the challenges to Iran’s security and regional stability after the sanctions regime lifting and settlement of the Syrian conflict. The main components of the foreign policy strategy and national priorities of the IRI with regard to the Middle East region as well as to the countries-allies are considered. It is methodologically reasonable to consider these issues on the basis of the defensive realism position, which allows the author to explore the features of Iran’s foreign policy. The author used scientific analytic methods (logical, contrastive-comparative, inductive-deductive, etc). A system approach made it possible to give an integral analysis of the multi-level system of Iran's involvement in international relations in the Middle East. It is emphasized that after the talks on the Iran nuclear deal between Iran and the P5+1, and the conclusion of the JCPOA (2015) Iran hasn’t changed its regional strategy. The author concludes that despite the short-term effects that have taken place in the regional dimension after the conclusion of the JCPOA, this agreement is still not a decisive factor determining the direction of regional changes. In the long term the situation in the Middle East and the role of Iran in it will be determined by internal conditions and regional trends, as well as the factor of international involvement in regional processes.