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S100A8\/A9 plays an important role in inflammation and fibroblast activation. However, the role of S100A8\/A9 in IUA remains unclear. In this study, we collect normal and IUA endometrium to verify the expression of S100A8\/A9. Human endometrial stromal cells (hEnSCs) are isolated to evaluate fibrosis progression after S100A8\/A9 treatment. A porcine IUA model is established by electrocautery injury to confirm the therapeutic effect of menstrual blood-derived stromal cells (MenSCs) on IUA. Our study reveals increased S100A8\/A9 expression in IUA endometrium. S100A8\/A9 significantly enhances hEnSCs proliferation and upregulates fibrosis-related and inflammation-associated markers. Furthermore, S100A8\/A9 induces hEnSCs fibrosis through the RAGE-JAK2-STAT3 pathway. Transplantation of MenSCs in a porcine IUA model notably enhances angiogenesis, mitigates endometrial fibrosis and downregulates S100A8\/A9 expression. 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