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Objective Explore the immunoregulatory effect of scal+ MSCs subset on acute graft versus host disease.Method A mouse model of MHC-mismatched HSCT was established by transplanting BM and spleen cells from C57BL/6(donor, H-2b) mice to BALB/C(recipient,H-2d) mice previously irradiated with a dose of 8.0 Gy.To explore the effect of scal+ MSCs subset on GVHD, the scal+ cells were administered intravenously at the same time as BM and spleen cells transplantation.The mice were divided into 3 groups in each experiment∶ BM+ spleen group, mice received 1×107 BM and 6×106 spleen cells from C57BL/6 donor ; Scal+BM+spleen group, mice received 1× 107 BM and 6× 106 spleen cells plus 8× 104 Scal+ MSCs from C57BL/6 donor; control group, mice received 1 × 107 BM form BALB/C.To compare the degrees of acute GVHD in each group, the loss of body weight and survival proportion were observed and clinical scores were graded with a scoring system.The infiltration of donor derived CD4+ T cells and CD8+ T cells in spleen and lymph node was detected by flow cytometry analysis.Results The loss of body weight was more moderate and survival propotion was higher in Scal+BM+spleen group.The infiltration of donor derived CD4+ T cells and CD8+ T cells in sleen and lymph node was reduced in Scal+BM+spleen group compared to BM+spleen group.Conclusion Our results showed that non-cultured scal+ MSCs decreased the severity of acute GVHD.