Abstract： Objective： To observe the clinical effect of Huoxue Shengji Prescription combined with closed negative pressure wound drainage on varicose veins of lower extremity with ulcer. Methods：A total of 88 patients with varicose veins of lower extremity with ulcer admitted to Jiaxing Hospital of Traditional Chinese Medicine from January 2022 to October 2023 were selected and randomly divided into the control group and the observation group， with 44 patients in each group.The control group was given 0.9% of sodium chloride solution combined with closed negative pressure drainage， and the observation group was given Huoxue Shengji Prescription combined with closed negative pressure drainage. Both groups were treated for two weeks. The clinical effects in the two groups were evaluated； the wound symptom scores， angiogenesis indexes and levels of inflammatory factors before and after treatment were compared between the two groups. Results： After treatment， the total effective rate was 88.64%（39/44） in the observation group，which was higher than that of 70.45%（31/44） in the control group （P＜0.05）. After treatment，the wound symptom scores in the two groups were decreased when compared with those before treatment （P＜0.05），and the wound symptom score in the observation group was lower than that in the control group （P＜0.05）. After treatment， the levels of endostatin （ES） in the two groups were reduced when compared with those before treatment，and the level in the observation group was lower than that in the control group （P＜0.05）. The levels of basic fibroblast growth factor（ bFGF） and vascular endothelial growth factor（ VEGF） in the two groups were elevated when compared with those before treatment，and the levels in the observation group were higher than those in the control group （P＜0.05）. After treatment，the levels of tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β） and interleukin-6 （IL-6） in the two groups were declined when compared with those before treatment （P＜0.05），and the levels of TNF-α，IL-1β and IL-6 in the observation group were lower than those in the control group （P＜0.05）. Conclusion： Huoxue Shengji Prescription combined with closed negative pressure wound drainage has a significant curative effect in the treatment of varicose veins of lower extremity with ulcer，which can promote wound healing and microvascular endothelial growth， accelerate the formation of blood vessels，and reduce the body's inflammatory responses.