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Objective: To investigate the effect of rapamycin on cognitive function of Operative Cognitive Dysfunction rats induced by anesthesia and explore its possible mechanism. Methods: Wistar rats were intraperitoneally injected with 70 mg/kg ketamine for 7 days to establish POCD model after anesthesia. The model rats were randomly divided into model group, rapamycin group, everolimus positive group and 3-methyladenine group. The rats in the model group were intraperitoneally injected with the same amount of normal saline, rapamycin group was intraperitoneally injected with 3.5mg/kg rapamycin, everolimus positive group was intraperitoneally injected with 5.0mg/k everolimus, 3-methyladenine group was intraperitoneally injected with 3.5mg/kg rapamycin + 2.0mg/kg3-methyladenine for 7 days. Morris water maze was used to measure the retention time, the number of times of platform crossing and the latency time of working memory. Ferritin H, ferritin L, S100 β, Beclin 1 were determined by ELISA, and P13K, p-Akt, p-mTOR, 4EBP1 were determined by Western blot. Results: In rapamycin group, the retention time and the number of crossing platform were significantly higher than those in the model group(t=6.645,P<0.01;t=5.961,P<0.01), and the latency time of working memory was significantly lower than that in the model group(t=3.799,P<0.01); In rapamycin group, ferritin H, ferritin L, S100 β were significantly lower than that in the model group(t=3.248,P<0.01;t=4.137,P<0.01;t=2.915,P<0.01).3-methyladenine group was significantly lower than rapamycin group in the retention time and the number of times of platform penetration(t=5.138,P<0.01;t=4.437,P<0.01), and the latency time of working memory was significantly higher than rapamycin group(t=2.808,P<0.05); Ferritin H, ferritin L and S100 β in 3-methyladenine group were significantly higher than those in pamamycin group(t=2.247,P<0.05;t=3.330,P<0.01;t=2.119,P<0.05). In rapamycin group, P13K and p-Akt protein levels did not change, p-mTOR protein and P- 4EBP1 expression was down-regulated, after using 3-methyladenine, P-mTOR protein and P- 4EBP1 protein was up-regulated. Conclusions: Rapamycin can improve the cognitive function of POCD rats induced by anesthesia, and its mechanism may be related to the activation of mTOR signaling pathway by rapamycin to promote autophagy.