Objective To investigate the neuroproteetive effect of Rhubarb extract (RE) on cerebral ischemia-reperfusion injury in mice and its mechanism.Methods Twenty-eight male ICR mice were randomly divided into sham operation,ischemia-reperfusion,low-dose RE (100 mg/kg),and high-dose RE (100 mg/kg) groups.A model of middle cerebral artery occlusion and reperfusion in mice was induced by the suture method.The drug intervention groups were given intragastric RE administration (once a day) on the third day before model preparation,and the same volume of normal saline was injected into mice of the cerebral ischemia-reperfusion group.The volume of cerebral infarction was detected by triphenyltetrazolium chloride staining.The neuron-specific nuclear protein (NeuN),glial fibrillary acidic protein (GFAP),and ionized calcium binding adapter 1 (IBA-1) were used as markers of the ischemic cortical neurons,astrocytes,and microglial cells,respectively,and detected by inmunohistochemistry.The expression levels ofsuperoxide dismutase (SOD)-1,SOD-2,and catalase (CAT) in ischemic cortex were detected by Western blot analysis.Results Compared with the cerebral ischemia-reperfusion group,the neurological function score of the high-dose RE group was significantly reduced,the infarct volume was significantly reduced,and the number of neurons in the ischemic cortex was increased significantly,and the activation degree of astrocytes and microglia was decreased significantly (all P ＜0.05),the expression levels of SOD-1,SOD-2,and CAT were increased significantly (all P＜ 0.05);in contrast,there was no significant difference between the low-dose RE group and the cerebral ischemia-reperfusion group.Conclusions High-dose RE may play a protective role for cerebral ischemia-reperfusion mice through anti-oxidative mechanism.