Objective To observe and evaluate the protective effects of rapamycin on neuronal damage after focal cerebral ischemia-reperfusion in rats. Methods A total of 52 male SD rats were randomly divided into control group and experimental group（ rapamycin intervention group）， with 24 rats in each group， and the other 4 rats were assigned into sham-operated group. The model of focal ischemia-reperfusion was prepared by Longa's method. Each index was observed at the 4th， 6th， 12th， 24th， 72nd hour and the 7th day after reperfusion for 3 hours. The experimental group was injected with rapamycin（ 1 mg/kg） intraperitoneally before establishing the cerebral infarction model. The sham-operated group did not plug the thread， and the rest of the process was same with the control group. The changes of brain tissue were observed by TTC staining. Changes of Bcl-2， Caspase-3 and autophagy related prtein LC-3 were detected by immunohistochemistry （immunofluorescence）. Results There was no ischemia detection in TTC staining sham operation. After 3 hours of ischemia， the lesion side brain tissue was pale， and the lesions in the experimental group were smaller than those in the control group. The score of neurological deficit of the experimental group at the 6th， 12th and 24th hour after reperfusion was lower than that of the control group（ P＜0.05）. The expression of caspase-3 increased significantly at the 4th hour after reperfusion and peaked at 24h， and the expression of caspase-3 of experimental group at the 6th， 24th hour and the 7th day was significantly lower than that of control group， and the difference was statistically significant（ P ＜ 0.05）. The expression of Bcl-2 increased at the 4th hour after reperfusion， and peaked at the 24th hour after reperfusion. The reperfusion at the 4th， 6th， 12th and 24th hour of the experimental group was significantly higher than that of the control group（ P ＜ 0.05）. The expression of LC-3 of the experimental group was significantly higher than that of the control group . Conclusions Rapamycin can promote LC-3 expression to inhibit apoptosis， reduce the expression of Caspase-3 and increase the expression of Bcl-2， so as to reduce the injury caused by ischemia， which has a definite effect on the recovery of neurological function after ischemia in rats.