〔Abstract〕 Objective To investigate the regulation effect of berberine(BBR) on abnormal proliferation of mesangial cells(MCs) induced by high glucose(HG) and its possible mechanism. Methods MCs were cultured in vitro. The experiment was divided into control group, HG model group and BBR different concentration gradient action group(30, 60, 90 μmol/L). CCK-8 method was used to detect cell viability; high content system imaging method was used to detect cell proliferation; laser confocal method was used to detect extracellular matrix(ECM) deposition protein collagen Ⅳ(Col-Ⅳ) and fibronectin(FN) expression; Western blot was used to detect extracellular signal-regulated kinase(ERK),p-ERK, Phosphorylated mitogen-activated kinase 1(p-MSK1), IκB, p-IκB, p65, p-p65 protein expression. Results The results of CCK-8 method showed that BBR(30,60,90 μmol/L) could regulate the proliferation of MCs; high-content system imaging results showed that BBR(30,60,90 μmol/L)could inhibit the abnormal proliferation of MCs induced by HG; the results of laser confocal experiments showed BBR(90 μmol/L) could reduce the expression of ECM deposition proteins Col-Ⅳ, FN; Western blot results showed that BBR(30,60,90 μmol/L) could reduce the expression of p-ERK, p-MSK1, p-IκB,p-p65 protein. Conclusion BBR may regulate the ERK/NF-κB signaling pathway of MCs and improve the abnormal proliferation of MCs induced by HG.