Objective To study the protective effect of bilobalide on cerebral ischemia reperfusion injury under hyperglycemia in rats and explore the possible mechanisms. Methods Rats were given 50% glucose （6 ml/kg）by intraperitoneal injection to get acute hyperglycemia model. Cerebral ischemia reperfusionmodel was made by intraluminal monofilament. 40 rats were randomly divided into hyperglycemia+sham opera-tion group （sham group，n=8），hyperglycemia+MCAO group （model group，n=8），hyperglycemia+MCAO+bilo-balide group （bilobalide groups，n=24）. Bilobalide groups were then divided into three dose groups （2.5，5 and 10 mg/kg，n=8）. The bilobalide groups were given intraperitoneal injection for 3 d and 1 h before cerebral isch-emia. After blocking middle artery for 2 h and reperfusion for 24 h，neurological deficit scores，cerebral infarc-tion volume，brain water content，AQP4 mRNA，SOD activity，MDA content，NE，DA and 5-HT expression were detected. Results Rats in bilobalide （5，10 mg/kg）group showed significantly relieved neurological deficit scores，reduced cerebral infarction volume，decreased brain water content，down-regulated AQP4 mRNA ex-pression，up-regulated SOD activity，reduced MDA content and improved content of NE，DA and 5-HT，com-pared to those in model group（P＜ 0.05）. Conclusions Bilobalide could relieve cerebral ischemia reperfusion injury of cerebral ischemia reperfusion rats under acute hyperglycemia.