〔Abstract〕 Objective To explore the effects of autophagy activation on propofol-induced apoptosis in hippocampal neurons. Methods Primary hippocampal neurons were extracted and isolated from fetal rats and randomly divided into control group, propofol group, rapamycin group and chloroquine group. 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2 H-tetrazolium-5-carboxanilide(XTT) and flow cytometry were used to detect apoptosis, and Western blot was used to detect the expression of autophagy and apoptosis-related proteins. Then, aged rats were randomly divided into control group, propofol group, rapamycin group and chloroquine group. 100 mg/kg propofol was used for continuous anesthesia for 1 week, during which 50 mg/kg rapamycin and 10 mg/kg chloroquine were treated. Morris water maze was used to detect cognitive function, TUNEL staining was used to detect apoptosis, Golgi staining was used to observe autophagy, and Western blot was used to detect autophagy-related apoptosis-related protein expression. Results In vitro, rapamycin obviously reversed the apoptosis caused by propofol, but chloroquine had no effect. Compared with propofol group, the expression of microtubule-associated protein light chain 3 Ⅱ/microtubule-associated protein light chain 3 I(LC3 Ⅱ/LC3 Ⅰ) and Beclin-1 in the rapamycin group increased, but the expression of apoptotic proteins Cleaved-caspase-3 and Bax decreased.In vivo, compared with propofol group, the water maze escape latency of the rapamycin group reduced. In addition, the number of TUNEL-positive cells and autophagosomes in the rapamycin group decreased. Furthermore, the expression of mammalian target of rapamycin(mTOR) in the rapamycin group decreased, and the expression of LC3 Ⅱ/LC3 Ⅰ and Beclin-1 increased, as well as the expression of Cleaved-caspase-3 and Bax decreased. But chloroquine had no effect on autophagy and apoptosis-related proteins. Conclusion Rapamycin can further activate autophagy by inhibiting the activation of mTOR signal, ameliorate the neuronal apoptosis caused by propofol, which will lead to the improvement of the cognition in rats.