Abstract: The therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with intestinal probiotics on the wound healing of diabetic mice and its potential mechanism were explored. Twenty-five male C57BL/6J mice were selected and induced to develop diabetes by intraperitoneal injection of streptozotocin (STZ), and a back skin wound model was constructed. Then, the diabetic mice were randomly divided into 5 groups (n=5), namely the blank control group, the model group, the hUCMSCs treatment group, the probiotic treatment group, and the hUCMSCs combined with probiotic treatment group. The wound healing status was photographed and recorded at days 0, 3, 6, 9, and 12, and the differences in the non-healing rate of the wounds in each group were analyzed. HE and Masson staining were used to observe the histological changes and collagen deposition; CD31 immunofluorescence staining was used to detect angiogenesis; Collagen I immunohistochemical staining was used to evaluate the formation of type I collagen; ELISA was used to detect the expression levels of pro-inflammatory factors (TNF-α, IL-1β, IL-6) and anti-inflammatory factor (Arg1) in the wound tissue. The results showed that on the 12th day after modeling, all treatment groups observed a significant reduction in wound area, with the combined treatment group showing the most obvious wound contraction and the fastest healing speed; HE and Masson staining showed that in each treatment group, the process of epithelialization and the deposition of collagen tissue increased, and the combined treatment group had the best effect; immunofluorescence and immunohistochemistry showed that compared with the model group, the expression of CD31 and Collagen I in each treatment group was significantly increased, with the combined treatment group having the most expression; ELISA showed that the Arg1 expression level in the hUCMSCs combined with probiotic treatment group was higher than that in other groups, but the difference was not statistically significant (P>0.05), and compared with the model group, the contents of TNF-α, IL-1β, and IL-6 in each treatment group were all reduced, with the combined treatment group having the lowest content. The above results preliminarily indicate that the combined treatment of hUCMSCs and intestinal probiotics can accelerate the wound healing of diabetic mice through mechanisms such as promoting angiogenesis, enhancing collagen deposition, and regulating the inflammatory microenvironment, and its efficacy is significantly better than single treatment. This study provides a new potential strategy for the clinical treatment of diabetic foot.