Objective To explore the effect of picrodideⅡ on the expressions of Caspase-3 in brain tissue following cerebral ischemic reperfusion injury in rats. Methods The middle cerebral artery occlusion reperfusion models were established with intraluminal thread methods in rats. Picrodide Ⅱ (10 mg/kg) was injected from tail vein for treatment. The neurological function was evaluated with Bederson's test. The brain structure was observed by hematoxylin-eosin (HE)stain and the apoptosis were counted by TUNEL immunofiuorescence assay. The expressions of Caspase-3 were detected with immunohistochemical and enzyme linked immunosorbent assay. Results After ischemia for 2 h and reperfusion for 22 h, the rats showed neurological function deficit. The expressions of Caspase-3 and the number of apoptotic cells in brain tissue increased significantly than those in the sham operative group (P＜ 0.01). In picroside, the Bederson's scores, the expressions of Caspase-3 and the number of apoptosis cells were significantly lower than those in the negative control group(P＜0.01).Conclusion Picroside Ⅱ might reduce the expressions of Caspase-3 to inhibit the neuronal apoptosis induced by cerebral ischemia reperfusion injury and improve the neurological function of rats.