Graft-versus-host disease (GVHD) remains one of the most important barriers to bone marrow transplantation (BMT) and quality of life. Peritoneal-derived cells (PCs) can regulate immune function.The GVHD mouse model, which was established by injection with T-cell depleted bone marrow cells and spleen cells, was treated with donor PCs. The survival time, weight, GVHD score, and pathological organ damage were used to assess the efficacy of PCs. Various cytokines (e.g., TNF-α, IFN-γ, IL-2, IL-17, IL-15, IL-4, IL-10, and TGF-β) and immunocytes (e.g., CD4+, CD8+, Treg, and NK cells) were employed to investigate the preliminary mechanism. The cytokine levels were tested via Luminex liquid chips, real-time PCR, and Western blotting, and the proportion of each T-cell subpopulation was detected via flow cytometry. One-way Analysis of Variance (ANOVA) followed by Tukey's post-test was employed to perform multiple comparisons, and Kaplan-Meier method was used to perform survival analysis.Compared to the saline group, the PC group harbored a significant reduction in pathological damage to the colon and small intestine, a longer survival time, and a lower GVHD score. The mice in the PC group had significantly higher levels of TGF-β, IL-10, and IL-4 and lower levels of IFN-γ, TNF-α, and IL-15 than those in the saline group. In the PC group, CD8+ and Th1 ratios decreased, while CD4+, Th2, NK, and Treg ratios increased.Donor PCs can attenuate GVHD caused by MHC-incompatible BMT by regulating cytokine levels and immunocyte ratios.Copyright © 2022 Elsevier B.V. All rights reserved.