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PURPOSE Through the study of regulatory T cells (Tregs), we found a possible way to promote the healing of diabetic foot ulcers (DFUs) with maggot treatment and investigated the associated mechanism. METHODS Immunohistochemistry was used to examinetissues from DFU patients treated with or without maggot debridement therapy (MDT). The expression of the signature Treg molecule Foxp3, interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), and interferon regulatory factor 4 (IRF-4) in patients with DFU treated with or without MDT was tested by real-time PCR (RT-PCR). CD4+ T cells from mouse spleen cells were cocultured in vitro with maggot excretions/secretions (ES), and Foxp3, IL-10, TGF-β, and IRF-4 levels were measured by RT-PCR. RESULTS Foxp3 expression was obviously increased in DFU patients treated using MDT but less pronounced in those treated without MDT (P < 0.05). Foxp3, IL-10, TGF-β, and IRF-4 gene expression levels were higher in DFU patients treated with MDT than in those treated without MDT. Moreover, in vitro coculture of mouse spleen cells with ESs produced results consistent with the in vivo results (P < 0.001). CONCLUSION MDT/ESs can obviously upregulate the Treg level and may affect DFU healing in different ways, suggesting a new direction for the future treatment of DFU.