〔Abstract〕 Objective To explore the protective effect and mechanism of dapagliflozin on palmitic acid-induced human renal tubular epithelial cells. Methods Human renal tubular epithelial cells were culturedin vitroand divided into normal control(CON) group, palmitic acid(PA) group, palmitic acid+dapagliflozin(PA+Dapa) group, and dapagliflozin(Dapa) group.After 24 hours of intervention, CCK-8 method was used to detect cell proliferation, DCF immunofluorescence was used to detect intracellular reactive oxygen species(ROS),JC-1 fluorescence was used to detect mitochondrial membrane potential, the kit detected the levels of superoxide dismutase(SOD) and malonaldehyde(MDA) in cells, Western blot detected the levels of apoptotic proteins caspase3,Cleaved caspase3 and cytochrome C(Cyto C),and Hoechst33258 fluorescence detection apoptosis. Results Compared with CON,the PA group decreased cell proliferation, increased ROS level, decreased mitochondrial membrane potential, decreased SOD level and increased MDA level, increased levels of apoptotic proteins caspase3 and Cleaved caspase3,and increased expression of Cyto C,the apoptosis level detected by Hoechst33258 increased, and the differences were statistically significant(P<0.05);the above indicators in the Dapa group were not significantly different from those in the CON group; compared with the PA group, the cell proliferation in the PA+Dapa group increased.The level of ROS decreased, the level of mitochondrial membrane potential increased, the level of SOD increased, the level of MDA decreased, the expression of apoptotic proteins caspase3,Cleaved caspase3,and Cyto C decreased, and the level of apoptosis detected by Hoechst33258 decreased.The difference was statistically significant(P<0.05). Conclusion Dapagliflozin has a protective effect on human renal tubular epithelial cells induced by palmitic acid.The mechanism may be related to the improvement of mitochondrial function and the level of oxidative stress.