Objective To explore the effect and probable mechanism of rosuvastatin preconditioning on inflammatory cytokines interleukin (IL)-1β，IL-6 and tumor necrosis factor α (TNF-α) release in vascular smooth muscle cells (VSMCs) of middle cerebral artery after ischemia-reperfusion. Methods Thirty-six healthy SD rats were randomly assigned into three groups：sham operation group，focal cerebral ischemia-reperfusion group and rosuvastatin preconditioning group. There were 12 rats in each group. At the 24th hour of reperfusion after middle cerebral artery occlusion (MCAO) for 2 hours, the mRNA and protein expression of IL-1β，IL-6 and TNF-α release in VSMCs of middle cerebral artery were detected by Real-time PCR and Western blotting，respectively.Also，the mRNA and protein expression of nuclear factor κB (NF-κB) were measured by Real-time PCR and Western blotting. Results At the 24th hour of reperfusion after MCAO for 2 hours，the mRNA and protein expression of IL-1β，IL-6 and TNF-α were markedly up-regulated in rats of model group；rosuvastatin preconditioning can significantly inhibited overexpression of IL-lβ，IL-6 and TNF-α at the mRNA and protein levels. And the decreasing of mRNA and protein expression of NF-κB was also found in this study. Conclusion Rosuvastatin preconditioning can decrease the release of inflammatory cytokines IL-1β，IL-6 and TNF-α in VSMCs of MCA. It can relieve the inflammatory injury after ischemia-reperfusion in brain. The effect of rovastatin on IL-1β，IL-6 and TNF-α may be related to the reduction of the expression of NF-κB in VSMCs.