Objective To investigate the neuroprotective effect of miR-138 on cognitive impairment induced by sevoflurane anesthesia. Methods 7-week-old SD rats were randomly divided into control group，sevoflurane group，sevoflurane+NC mimic group， sevoflurane+miR-138 mimic group，sevoflurane+miR-138 mimic vector group, sevoflurane+miR-138 mimic+pcDNA-LCN2 group. A rat model of cognitive impairment induced by sevoflurane was constructed. The rats induced by sevoflurane were injected with 10 μL miR-138 mimic and NC mimic lentivirus suspensions. Morris water maze experiment was used to analyze the incubation period，cross-stage time and swimming speed. HE staining was used to detect the pathological changes of hippocampal neurons. TUNEL staining was used to detect the apoptosis of hippocampal neurons. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect miR-138 and lipocalin 2 (LCN2) mRNA level expression. The dual luciferase reporter gene system was used to detect the relationship between miR-138 and LCN2. Western blotting was used to detect LCN2, cleaved caspase-3, cleaved caspase-9, Bax, Bcl-2, p-JAK2 and p-STAT3 protein levels. ELISA test was used to detect IL-6, TNF-α, IL-1β in hippocampus. Results Sevoflurane group compared with control group, miR - 138 expression level was significantly reduced (P < 0.05). The number of hippocampal neuronal damage and apoptosis were significantly increased, the protein levels of cleaved caspase-3, cleaved caspase-9 and Bax were significantly increased, and the protein levels of Bcl-2 were significantly decreased. IL beta, TNF-1 alpha, IL-6 levels, p-JAK2 and p-STAT3 protein levels (P<0.05). Compared with sevoflurane+miR-138 mimic group, the escape latency of rats in sevoflurane+miR-138 mimic group was decreased, The Times of crossing platform was increased, neuronal pathological damage was attenuated, and the number of hippocampal neuronal apoptosis was significantly decreased. Cleaved caspase 3, cleaved- caspase 9- and Bax protein levels are low, the Bcl-2 levels, IL-1 beta, TNF-alpha, IL-6 levels drop, p-JAK2 and p-STAT3 protein levels (both P<0.05). Dual luciferase reporter gene showed LCN2 is miR-138 target genes, overexpression of LCN2 can significantly reversed miR-138 for cognitive impairment induced by sevoflurane apoptosis in rats (P< 0.05). Conclusion miR-138 targeting LCN2 has a neuroprotective effect on sevofluraneinduced cognitive impairment through JAK2/STAT3 pathway.