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OBJECTIVE:To investigate the efficacy of Xia-okeping(XKP)-containing serum on the prolifera-tion of high-glucose-induced mesangial cells(MCs)and the potential underlying mechanism.METHODS:XKP-containing serum was prepared by the intragastric administration of XKP in rats.HBZY-1 cells were cultured with normal glucose(NC group),high glucose(HG group),and high glu-cose with different XKP concentrations.Cell prolifer-ation was assessed by the 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide assay,and the cell cycle distribution was detected by flow cytometry.The expression of p38 mitogen-activat-ed protein kinase(p38MAPK)pathway compo-nents in MCs was detected by Western blotting and quantitative real-time polymerase chain reaction.RESULTS:The MC proliferation level in the high-glucose group was significantly higher than that in the normal control group,and XKP sup-pressed the HG-induced proliferation of MCs dose dependently.Moreover,flow cytometry revealed that XKP blocked cell cycle progression by inducing cell cycle arrest in G1 phase and inhibiting S phase entry.XKP down-regulated the protein and mRNA expression of p38MAPK in MCs(P＜0.05 vs HG).CONCLUSION:The present study demonstrated that XKP-containing serum inhibits high-glucose-induced proliferation of MCs by causing cell cycle arrest at G1 phase and inhibiting S phase entry.The underlying mechanism involves the down-regula-tion of the p38MAPK signaling pathway,providing a theoretical basis for the use of XKP to treat diabet-ic kidney disease.