Objective To explore the therapeutic effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on bleomycin-induced skin scar in mice and its possible mechanism. Methods BM-MSCs were isolated and purified from C57BL/6 mice by direct adherence method. Thirty male C57BL/6 mice were randomly divided into control group, skin scar model group and BM-MSCs administration group (10 each). The mice in skin scar model group and BM-MSCs administration group were subcutaneously injected with 1ml bleomycin (1mg/ml), 3 hours later, the mice in BM-MSCs administration group were subcutaneously injected with 1×106 BM-MSCs suspended in 1ml phosphate-buffered saline (PBS) and in skin scar model group with 1ml PBS, while the mice in control group were subcutaneously injected with 1ml PBS at the aforementioned two time points respectively every day. After 4 weeks, the mice were sacrificed and fresh skin specimens were harvested for preparation of frozen section, and then the expression of transforming growth factor β1 (TGF-β1) was determined by immumofluorescence method. For the rest skin tissues, 4% paraformaldehyde-fixed and paraffin-embedded sections (5μm) were obtained, and the histopathological changes were observed with HE and Masson's Trichome staining, while the expression of α-smooth muscle actin (α-SMA) was observed by immunohistochemical method. Results The skin scar significantly alleviated, the collagen thickness of dermis significantly decreased, and the expression of TGF-β1 and α-SMA reduced in BM-MSCs administration group when compared with those in skin scar model group. Conclusion The transplantation of BM-MSCs could inhibit the bleomycin-induced skin scar formation in mice, and the mechanism may be related with the regulation of TGF-β1 expression.