Purpose: The healing process is impaired in diabetic wounds like the other types of chronic wounds. Cytokines, and growth factors are valuable candidates for determination of wound vitality or duration. The aim of this study is to introduce a beneficial method to stop the inflammatory phase and infection in the wound healing process for accelerating the treatment of diabetic foot ulcers. Methods: As a randomized controlled trial, 44 patients with diabetic foot ulcers were selected and randomized. Twenty-two patients received standard care and rest of them received SC (standard care) + CAP (cold atmospheric plasma), n = 22). Clinical examination was performed to assess the status of peripheral nerves and arteries for all patients. Cold plasma jet was used as a source of helium gas plasma generator. Plasma was irradiated on the wound 5 min, 3 times a week for 3 consecutive weeks. Results: Applying a plasma jet was effective in wound healing. The level of inflammatory cytokines was changed. Moreover, after applying plasma the mean expression of these variables was significantly decreased (P = 0.001). Following the plasma treatment, the level of cytokines such as IL-1 (39.44 ± 7.67), IL-8 (368.30 ± 82.43), INF-γ (17.03 ± 2.62), TNFα (22.75 ± 4.02) has decreased, inflammatory factors have ameliorated over three weeks, and accelerate wound healing. After CAP exposure, the mean of the mean fraction of bacterial load counts was significantly decreased. Conclusion: The effect of plasma irradiation on infectious diabetic foot ulcer was decreased bacterial load then accelerated wound healing by effecting on inflammatory phase in diabetic foot ulcers.