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Objective To explore the effect of miR-433 on oxidative stress and cognitive function in the hippocampus of rats with postoperative cognitive impairment (POCD) and its mechanism of action. Methods Rats were randomly divided into 4 groups, control group, POCD group, POCD+NC mimic group, and POCD+miR-433 mimic group. A rat POCD model was constructed, and the expression of miR-433 in hippocampal tissue of POCD rats was detected by real-time fluorescence quantitative PCR assay (RT-qPCR). Morris Water Maze test was used to evaluate the cognitive function of rats. Hematoxylin and Eosin (HE) staining was used to detect histopathological changes in hippocampus. TUNEL staining was used to detect cell apoptosis. The level of oxidative stress was detected by enzyme-linked immunosorbent assay (ELISA). Dual luciferase reporter gene system was used to detect the targeting relationship between miR-433 and JAK2. Western blotting was used to detect the expression of cleaved caspase-3, Bad, Bcl-2, JAK2, p-JAK2, STAT3, and p-STAT3 proteins in the hippocampus tissues. Results Compared with the control group, miR-433 expression in hippocampus tissues of rats in the POCD group was significantly reduced. The evasion latency was prolonged. The number of crossing the target platform was reduced. Neuronal cells in the POCD group were disordered. The number of cells was significantly reduced. The apoptosis rate of neuronal cells was significantly increased. Cleaved caspase-3 and Bad protein expression was significantly increased. Bcl-2 protein expression and superoxide dismutase (SOD) level significantly decreased. Malondialdehyde (MDA) level increased significantly. The difference was statistically significant (P ＜ 0. 05). Compared with the POCD + NC mimic group, the expression of miR-433 in hippocampus tissues of rats in the POCD + miR-433mimic group was significantly higher, the escape latency was shortened, the number of crossing the target platform was increased, the arrangement of cells in the hippocampus was more regular. The apoptosis rate of neuronal cells was significantly lower, and the rate of neuronal cell apoptosis was significantly reduced. The expression of cleaved caspase-3 and Bad protein expression was significantly decreased. Bcl-2 protein expression was significantly increased, SOD level was significantly increased, and MDA level was significantly decreased. The results of dual luciferase reporter gene assay showed that JAK2 was the target gene of miRNA-433, and compared with POCD + miR-433 mimic + Vector group, the hippocampal tissues of rats in POCD + miR-433mimic + pcDNA-JAK2 group showed significantly lower expression of JAK2, p-JAK2, p-STAT3, cleaved caspase-3, Bad protein, and MDA levels were significantly increased, while Bcl-2 protein and SOD levels were significantly decreased. The difference was statistically significant (P ＜ 0. 05). Conclusion MiR-433 inhibits oxidative stress through JAK2/STAT3 signaling pathway to prevent postoperative cognitive impairment in rats. [ABSTRACT FROM AUTHOR]