Objective: This study evaluated the efficacy and underlying mechanism of Shenghong (SH) liquid fumigation combined with alternating red/blue light therapy for Wagner grade 2-4 diabetic foot ulcers (DFUs).

Methods: Eighty patients with DFUs were randomized into four groups (n = 20 per group): control (basic care + fibroblast growth factor gel), red/blue (basic care + light), SH (basic care + SH fumigation) and SH + red/blue (basic care + SH fumigation + light). All participants received a two-week treatment. Outcomes included clinical efficacy, wound scores, ulcer shrinkage rate, pain scores, healing time, vascular endothelial growth factor (VEGF), interleukin-1 (IL-1) levels, and adverse events.

Results: Baseline characteristics were comparable (p > 0.05). After treatment, the SH + red/blue group demonstrated the lowest wound scores, the highest ulcer shrinkage rate, the lowest pain scores, the shortest healing time, the highest VEGF concentration, and the lowest IL-1 secretion. Mild adverse events occurred in 5–15 % of patients and resolved spontaneously.

Conclusion: The combination of SH liquid fumigation and alternating red/blue light therapy significantly accelerates the healing of Wagner grade 2-4 DFUs while exhibiting an acceptable safety profile.