OBJECTIVE: To explore the effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in granulation tissue of skin ulcers in rats with syndrome of blood stasis and qi deficiency. METHODS: Diabetic rats with back full-thickness skin lesion and syndrome of blood stasis and qi deficiency were divided in to five groups: untreated group, basic fibroblast growth factor (bFGF)-treated group, Yiqi Huayu Recipe (a recipe for replenishing qi and resolving stagnation)-treated group, Yiqi Recipe (a recipe for replenishing qi)-treated group and Huayu Recipe (a recipe for resolving stagnation)-treated group, and another eight normal rats served as normal control group. Immunohistochemical method and image analysis were used to test the expressions of HIF-1alpha and VEGF in granulation tissue of skin ulcers in rats with diabetes. RESULTS: In the untreated group, the expression of HIF-1alpha was significantly increased and the expression of VEGF was significantly decreased as compared with those in the normal control group (P<0.01). The expression of HIF-1alpha was obviously lower (P<0.01) and the expression of VEGF was significantly higher in the four drug treated groups as compared with those in the untreated group. In the Yiqi Huayu Recipe-treated group, the expression of HIF-1alpha was obviously lower than those in the bFGF-treated, Yiqi Recipe-treated and Huayu Recipe-treated groups (P<0.05 or P<0.01), and the expression of VEGF was significantly higher than that in the bFGF-treated group (P<0.01). CONCLUSION: Chinese herbs for replenishing qi and resolving stagnation can promote the wound healing in rats through reducing the expression of HIF-1alpha, accelerating the expression of VEGF in granulation tissue of skin ulcers in rats with diabetes and ameliorating the status of ischemia and hypoxia.