Objective　To investigate the effect of resveratrol (RES) on cognitive dysfunction and its effect on the silent information regulator 1 (SIRT1) /p53 pathway in aged rats induced by sevoflurane anesthesia. Methods　Thirty-two aged SD rats were divided into control group, sevoflurane group, RES group and SIRT1 inhibitor (EX527) group with eight rats in each group by random number table method. The control group inhaled 30% oxygen, and the sevoflurane group, RES group and EX527 group inhaled 3% sevoflurane and 30% oxygen for 4 consecutive hours. Before sevoflurane treatment, RES group was intraperitoneally injected with RES (100mg/kg), EX527 group was intraperitoneally injected with RES (100mg/kg) + EX527 (1 μg/kg) through tail vein, and control group and sevoflurane group were intraperitoneally injected with equal volume of normal saline.. Morris water maze was used to detect the cognitive function of rats. Hippocampal tissue was collected from rats and Hematoxylin-eosin (HE) staining was used to observe the morphology of the hippocampus. Then the levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) were detected by enzym-linked immunosorbent assay. Malondialdehyde (MDA) was determined by thiobarbituric acid method, superoxide dismutase (SOD) was determined by xanthine oxidase method and glutathione peroxidase (GSH-Px) determined by dithio-dinitrotoluidine method. The apoptosis rate was detected by TUNEL method, and the expression of apoptosis protein, SIRT1 and p53 in hippocampus were determined by Western blot method. Results　Compared with the control group, the escape latency of rats in the sevoflurane group was significantly increased on the 2nd to 5th day, the frequency of crossing the platform was significantly decreased (P0.05), and the levels of IL-6, IL-1β, TNF-α, MDA, apoptosis rate, Bax protein and Acetyl-p53/p53 in the hippocampus were significantly increased (P0.05), the activities of SOD and GSH-Px and the protein levels of Bcl2 and SIRT1 were significantly decreased (P0.05). Compared with the sevoflurane group, the escape latency of the RES group was significantly shortened on the 3rd to 5th day (P0.05), the frequency of crossing the platform was significantly increased (P0.05), and the IL-6, IL-1β, TNF-α, MDA, apoptosis rate, Bax protein and Acetyl-p53/p53 levels in the hippocampus were significantly decreased (P0.05), the activities of SOD and GSH-Px and the protein levels of Bcl-2 and SIRT1 were significantly increased (P0.05). Compared with the RES group, the escape latency of EX527 group was significantly increased at 4 to 5 days (P0.05), and the number of crossing platforms was significantly decreased at 4 to 5 days (P0.05), the levels of IL-6, IL-1β, TNF-α, MDA, apoptosis rate, Bax protein and Acetyl-p53/p53 levels in the hippocampus of rats were significantly increased (P0.05), while the activities of SOD and GSH-Px and the levels of Bcl-2 and SIRT1 protein were significantly decreased (P0.05). Conclusion　RES can improve cognitive dysfunction by regulating the SIRT1/p53 pathway in aged rats induced by sevoflurane anesthesia.