Objective：To investigate the expression of paeoniflorin（PF） on superoxide dismutase（SOD） and nuclear factor E2-related factor 2（Nrf2） in brain tissue of rats with middle cerebral artery occlusion at each time point and its neuroprotection. Methods：Totally 108 healthy adult male SD rats were randomized into sham operation group，model group，experimental group. Modified neurological severity score was detected at 3，6，12，24，48，72 h. Activity of SOD was detected by xanthine oxidase technique. Nrf2 mRNA and protein expression was detected by RT-PCR and Western blot. Results：Compared with those in sham operation group，the modified neurological severity score was significantly higher，SOD activity was significantly decreased and Nrf 2 expression was increased in model group with statistically differences（P<0.05）. Compared with those in model group，giving paeoniflorin（20 mg/kg） can make the modified neurological severity score decrease，SOD activity increase，Nrf2 expression increase with statistically differences（P<0.05）. Conclusion：Paeoniflorin can reduce the oxidative damage in brain tissues of rats with middle cerebral artery occlusion caused by free radicals by improving the capacity of body eliminating free radicals and increasing the expression of Nrf2.