One of the major events that occurred during the last years of the reign of Artabanus II، was the rebellion of Seleucia that lasted for seven years (36 - 42 AD). Since its establishment during the Seleukid، Seleucia – with its special geographical position alongside the Tigris in Mesopotamia –had special privileges such as autonomy، cultural، political and economic potentials. Seleucia had reserved such a position in the Parthian era until the first century when it rebelled against the Parthian king، Artabanus II – a rebellion which was eventually suppressed by Vardanes. It seems that the gradual change in Parthian attitudes towards the city، its population diversity، its ethnic conflicts، and Artabanus II’s interventions in affairs of Seleucia and the consequent reduction of its autonomy had been the most important reasons for such a rebellion. This paper seeks to explain and analyze the context as well as the causes and consequences of this rebellion.