Objective: To observe the effects of bufalin on overexpression of FN and CTGF in glomerular mesangial cells (MCs) of rat induced by high glucose,in order to explore the potential protective role of bufalin against diabetic nephropathy (DN). Methods: Cultured rat MCs were divided into 5 groups:control, high glucose(30 mmol/L),high glucose plus 5 × 10-9 mol/L bufalin,high glucose plus 5 × 10-8 mol/L bufalin,high glucose plus 5 × 10-7 mol/L bufalin. The cell toxicity of bufalin on MC were analyzed by Trypan blue method,expression of FN and CTGF was measured by RT-PCR and Western blot,respectively. Results: No cell toxicity was observed when bufalin was applied at the concentrations of 5 × 10-9 -5 × 10-7 mol/L. The expression of CTGF mRNA(P < 0.05) and protein(P < 0.05),FN mRNA level (P < 0.05) was significantly increased in the high glucose group compared with that of the control group. While the above-mentioned over-expression value induced by high glucose can be down-regulated by high,median,and low concentration bufalin in a concentration-dependent manner. Conclusion: Bufalin can inhibit the over-expression of FN caused by high glucose in MCs in a concentration-dependent maner,and the mechanism may be related to downregulating synthesis of CTGF,which indicates that bufalin deserves more investigation against DN.