Objective To observe the therapeutic effect of thunder-fire moxibustion combined with vacuum sealing drainage (VSD) on chronic lower extremity ulcer. Methods A total of 200 patients with chronic lower extremity ulcer admitted to Nanyang Municipal Hospital of Traditional Chinese Medicine from January 2022 to June 2025 were selected as the research subjects and randomly divided into a control group (100 cases treated with VSD alone) and an observation group (100 cases treated with VSD combined with thunder-fire moxibustion). The differences in therapeutic effects, wound healing rates, visual analogue scale (VAS) scores, inflammatory indicators [C-reactive protein (CRP), white blood cell count (WBC)], and growth factor expressions [vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1)] between the two groups were compared. Results After 14 days of treatment, the total effective rate and wound healing rate of the observation group were significantly higher than those of the control group (both P＜0.05). After 7 days and 14 days of treatment, VAS score, serum CRP and WBC levels in the observation group were significantly lower than those in the control group (all P＜0.05), while VEGF and TGF-β1 levels were significantly higher (both P＜0.05). Conclusion Thunder-fire moxibustion combined with VSD can effectively relieve pain and reduce inflammation, up-regulate the expression of growth factors, accelerate healing, and is worthy of promotion.