AIM: To investigate the effects of β-aescin on apoptosis induced by transient focal brain ischemia in rats. METHODS:Rats were pretreated with β-aescin for 7 d and then subjected to brain ischemia/reperfusion (I/R) injury induced by a middle cerebral artery occlusion. After 2 h ischemia and 24 h reperfusion, Hematoxylin-Eosin (HE) staining, in situ end-labeling of nuclear DNA fragmentation (TUNEL) were employed to determine the level of apoptosis. The expressions of caspase-3 and Bcl-2 in the cortex were determined by immunohistochemistry and Weste blot. The release of cytochrome c was analyzed by Weste blot. RESULTS: The increased numbers of HE- and TUNEL-positive staining cells were significantly observed at 24 h after reperfusion. The immunoreactivity was inhibited by β-aescin (30, 60 mg/kg) (P＜0.01 or P＜0.05 vs vehicle-treated). After cerebral I/R, cytochrome c was released into the cytosol and caspase-3 was activated, whereas Bcl-2 expression was inhibited. β-Aescin (30, 60 mg/kg) markedly inhibited the expression of caspase-3 and the release of cytochrome c, and up-regulated the expression of Bcl-2 (P＜0.05, P＜0.01 vs vehicle-treated). CONCLUSION: β-Aescin could potently inhibit caspase-3 activation and the release of cytochrome c, increasing the expression of Bcl-2 after cerebral I/R in rats. These findings on the inhibitory effects of β-aescin on brain ischemic injury-induced apoptosis might have important theoretical basis for the treatment on ischemic cerebrovascular diseases.