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Objective To observe the promotional effect of exosomes (MenSC-Exos) isolated from menstrual bloodderived mesenchymal stem cells (MenSCs) on the healing of skin wounds in SD rats and to investigate the mechanism. Methods MenSCs from healthy adult female volunteers were isolated and cultured, and MenSC-Exos were extracted. SD rats were randomly divided into the experimental and control groups, and mechanical wounds of the dorsal skin were made and treated with MenSC-Exos or PBS, respectively. We observed the wound healing and calculated the wound healing rate, used HE staining to observe the infiltration of inflammatory cells on the wound, used immunofluorescence to detect M1 and M2 macrophages, used immunohistochemistry to detect IL-6, IL-10, neovasculature, collagen type I, collagen type III in the tissues of the wound, and used Masson staining to detect the content and maturity of collagen on the wound. Fibroblasts were cultured and divided into the exosome and PBS groups, during which MenSC-Exos or PBS were added, respectively, and cell proliferation ability was detected by CCK-8 assay and cell migration ability by Scratch assay. Results The wound healing rate, type III collagen deposition rate, and collagen content of the experimental group were higher than those of the control group on postoperative day 7 and 14, and the type I collagen deposition rate was lower than that of the control group (all P<0. 05). The number of inflammatory cells and the M1/M2 ratio of the trauma on postoperative day 7 were lower in the experimental group than in the control group, and the number of M2-type macrophages was higher than that in the con‐ trol group (all P<0. 05). Compared with the control group, the experimental group had lower IL-6 expression and higher IL10 expression and vascular endothelial cell expression on the 3rd and 7th postoperative days of the trauma (all P<0. 05). The cell proliferation ability of the exosome group was higher than that of the PBS group from 1 to 5 days of culture, and the cell migration rate of the exosome group was higher than that of the PBS group at 24 h of culture (all P<0. 05). Conclusion MenSC-Exos can promote the healing of rat skin wounds, and the mechanism may be related to the regulation of inflammatory response, promotion of angiogenesis and fibroblast proliferation, and regulation of collagen remodeling. [ABSTRACT FROM AUTHOR]