Objective To investigate the protective effects of Empagliflozin (EMP) on the functional damage of mouse endothelial progenitor cells(EPCs)induced by oxidizedlow-densitylipoprotein (ox-LDL) and the related mechanisms. Methods Mouse bone marrow derived EPCs were extracted, separated, and cultured by density gradient centrifugation. Then, the cells were identified by the uptake of Dil-acetylated low density lipoprotein (Dil-ac-LDL) combined with FITC labeled ulex europaeus agglutinin-1(FITC-UEA-1) binding. EPCs were divided into control group, ox-LDL group and ox-LDL combined with different concentrations of EMP experimental groups, and simultaneously cultured for 72 hours. Cell viability, migration were analyzed by CCK-8 assay and Transwell assay, respectively. The cell apoptosis were measured by FITC-Annexin V/PI staining. The levels of vascular endothelial growth factor (VEGF), stromal-Derived factor-1 alpha (SDF-1α) in the medium were detected by enzyme linked immunosorbent assay (ELISA). The synthesis of nitric oxide(NO) was measured by flow cytometry. The protein expression of AMPK, p-AMPK, eNOS, p-eNOS in the EPCs were determined by Western blot. Results The extracted EPCs were cultured and identified as mouse bone marrow EPCs on day 7. Compared with control group, the cell viability of the ox-LDL group decreased, the migratory cell number decreased, the cell apoptosis rate increased, the VEGF and SDF-1αcontents decreased and the NO synthesis decreased（P＜0.05） Compared with ox-LDL group, the cell viability increased, the migratory cell number increased, the cell apoptosis rate decreased, the VEGF and SDF-1αcontents increased and the NO synthesis increased in EMP groups at different concentrations(P＜0.05).Besides, ox-LDL treatment could significantly inhibit the phosphorylation of AMPK and eNOS (P＜0.05), EMP treatment could improve the phosphorylation levels of AMPK and eNOS (P＜0.05) However, the protective effects of EMP could be significantly blocked by AMPK inhibitor (Compound C) (P＜0.05) Conclusion Empagliflozin can improve ox-LDL-induced EPCs dysfunction by regulating AMPK/eNOS signaling pathway