Non-healing diabetic ulcer causes the patient at much higher risk for lower extremity amputation. Several studies showed that both MSCs and EPCs can promote wound healing, increase angiogenesis and release of proangiogenic factors into the wound. Therefore, the objective of this study is to investigate whether the combination of EPCs and MSCs can enhance angiogenesis and wound healing in diabetic mice. Balb/c nude mice were divided into five groups. Group 1 was control group (Con; n=6). Group 2 was diabetic group treated with fibrin gel (DM; n=6). Group 3 was diabetic group injected with 1X106 cells MSCs (DM+MSCs; n=6). Group 4 was diabetic group injected with 1X106 cells EPCs (DM+EPCs; n=6). Group 5 was diabetic group injected with combined 0.5X106 cells MSCs and 0.5X106 cells EPCs (DM+MSCs+EPCs; n=6). Diabetic groups were induced by injection of streptozotocin (45 mg/kg i.p. daily for 5 days). At 7 weeks after, mice were anesthetized with sodium pentobarbital (55 mg/kg i.p.) and created bilateral full-thickness excisional skin wounds on the dorso-rostral back (0.6×0.6 cm2). On day 7 and 14 post-wound, the percentage of wound closure (%WC), the percentage of capillary vascularity (%CV), the neutrophil infiltrations and tissue vascular endothelial growth factor (VEGF) level were determined by using image analysis software, intravital fluorescence microscopy, H&E staining and ELISA, respectively. Values are means ± S.E.M., compared by ANOVA. The %WC in DM+EPCs, DM+MSCs, DM+MSCs+EPCs and Con increased significantly than DM group at day 7 (78.66 ± 2.29, 78.28 ± 4.16, 72.04 ± 4.12, 72.47 ± 4.52 vs. 55.65± 3.92; p<0.05) and day 14 (89.65 ± 1.07, 85.43 ± 1.58, 85.42 ± 0.64, 86.36 ± 0.84 vs. 80.42 ± 1.37; p<0.05). On day 7, the %CV in DM+EPCs, DM+MSCs, DM+MSCs+EPCs and Con were significantly increased than DM (22.86 ± 1.20, 21.42 ± 0.61, 27.44 ± 1.07, 19.95 ± 0.82 vs. 14.72 ± 1.49; p<0.05). The %CV of DM+EPCs+MSCs was increased significantly than DM+MSCs and DM+EPCs (p<0.05). On day 14, the %CV of DM+EPCs+MSCs was significantly higher than DM (24.92 ± 1.81 vs. 16.72 ± 1.39; p<0.05). Number of neutrophil infiltration in DM+EPCs, DM+MSCs, DM+MSCs+EPCs and Con increased significantly than DM at day 14 (12.40 ± 2.40, 11.60 ± 3.14, 14.60 ± 1.63, 13.00 ± 2.16 cells/field vs. 34.25 ± 4.59 cells/field; p<0.05). The VEGF levels in DM+EPCs, DM+MSCs, DM+MSCs+EPCs and Con were significantly higher than DM on day 7 (188.43 ± 28.09, 218.84 ± 27.50, 216.45 ± 53.01, 232.30 ± 44.09 pg/mg protein vs. 44.06 ± 10.70 pg/mg protein; p<0.05). In conclusion, the present study has demonstrated that the combined EPCs and MSCs can increase VEGF level and increased angiogenesis which lead to reduce number of neutrophil infiltration and enhanced wound healing in diabetic mice model.