〔Abstract〕 Objective To explore the effect of dapagliflozin(DAPA) on the function of rat endothelial progenitor cells(EPCs) culturedin vitroin a high glucose environment. Methods Bone marrow derived EPCs from sprague-dawley(SD) rats were identified by fluorescence staining. EPCs were divided into control group(CG group), high glucose group(HG group), high glucose + DAPA group(GD group) and high glucose + DAPA + LY294002 group(GDL group). MTT assay, flow cytometry, tubule formation assay were used to detect the viability, apoptosis, tubule formation ability of EPCs, respectively. Western blot was used to detect the protein expression of AKT/eNOS signaling pathway. Results Compared with CG group, cell viability, the ability to form tubules, the protein expression of p-AKT and p-eNOS, and the ratio of p-AKT/AKT and p-eNOS/eNOS in HG group significantly decreased(P<0.05), while the apoptosis rate of EPCs significantly increased(P<0.05). Compared with HG group, cell viability, the ability to form tubules, the protein expression of p-AKT and p-eNOS, and the ratio of p-AKT/AKT and p-eNOS/eNOS in GD group significantly increased(P<0.05), while the apoptosis rate of EPCs was significantly reduced(P<0.05). Compared with GD group, cell viability, the ability to form tubules, the protein expression of p-AKT and p-eNOS, and the ratio of p-AKT/AKT and p-eNOS/eNOS in GDL group significantly decreased(P<0.05), while the apoptosis rate of EPCs significantly increased(P<0.05). Conclusion DAPA can protect EPCs from high glucose induced functional damage through AKT/eNOS pathway.