Interleukin-17 (IL-17) is active in a variety of brain injuries, including ischemia. The objective of this study was to test the hypothesis that IL-17 potentiates neuronal injury after stroke. Increased expression of IL-17 and IL-17 receptor (IL-17R) in serum and cortex was evaluated by ELISA, RT-PCR and immunohistochemistry. In the in vitro model of oxygen-glucose deprivation (OGD), IL-17 showed a dose-dependent effect in promoting neuronal injury through IL-17-IL-17R combination which can be blocked by IL-17R/Fc chimera. Our results demonstrated the up-regulation of IL-17 and IL-17R following permanent middle cerebral artery occlusion and suggested that they contributed to stroke outcome.