OBJECTIVE: To investigate the efficacy of Xiaokeping(XKP)-containing serum on the proliferation 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 glucose with different XKP concentrations. Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,and the cell cycle distribution was detected by flow cytometry. The expression of p38 mitogen-activated protein kinase(p38 MAPK) pathway components 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 suppressed 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 m RNA expression of p38 MAPK in MCs(P < 0.05 vs HG).CONCLUSION: The present study demonstrated that XKP-containing serum inhibits high-glucoseinduced proliferation of MCs by causing cell cycle arrest at G1 phase and inhibiting S phase entry. The underlying mechanism involves the down-regulation of the p38 MAPK signaling pathway, providing a theoretical basis for the use of XKP to treat diabetic kidney disease.