〔Abstract〕 Objective To investigate the mechanism of action of remifentanil（RMZL） in alleviating lung ischemia-reperfusion injury（LIRI）in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α （HIF-1α)/NOD-like receptor thermal protein domain associated protein 3（NLRP3）pathway. Methods Rats were stochastically assigned into Control group，LIRI group，RMZL low-dose group，RMZL medium-dose group，RMZL high-dose group，and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine（DMOG）group，with 18 mice in each group. Mice in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group，LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model；rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum；rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluo ⁃rescence intensity of gasdermin D（GSDMD）and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α , NLRP3，cysteine-aspartic protease-1（Cleaved caspase-1），and gasdermin D-N（GSDMD-N）proteins in lung tissue. Results Compared to the Control group，the LIRI group showed disordered alveolar structure，thickened alveolar septa，and abundant in⁃ flammatory cell infiltration in rats. The lung wet/dry weight ratio，relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue，IL-1β , IL-18 levels，and HIF-1α , NLRP3，Cleaved caspase-1，and GSDMD-N proteins increased（P<0. 05）. For the LIRI group，rats in the RMZL low，medium，and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio，relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue，IL-1β , IL-18 levels，and HIF-1α , NLRP3，Cleaved caspase-1，and GSDMD-N proteins declined，and the RMZL high-dose group showed the most prominent trend（P<0. 05）. Compared with the RMZL high-dose group，rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration，along with in⁃ creased lung wet/dry weight ratio，relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue ，levels of IL-1β and IL-18 ，and protein expression of HIF-1α , NLRP3 ，Cleaved caspase-1 ，and GSDMD-N（P<0. 05）. Conclusion RMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.