Objective To investigate the effect of pentoxifyccine (FIX) on the pathway of high glucosd-induced expression of CTGF in mesangial cells. Methods Cultured rat mesangial celld were used to study the influence of different concentration of high glucose on the expression of TGF-β, CTGF, p-Smad2/3, Smad7 and FN in different exposure time. Furthermore the effect of high glucose plus TGF-β neutral antibody and different concentration of FIX on the obove expression was evaluated as well. Results High glucose could increase TGF-β, CTGF mRNA and protein expression in mesangial cells (P<0.05) in time-and dose-dependent manner, and at the same time p-Smad2/3 expression increased and Smad7 expression decreased (P<0.05).The blockage of TGF-β could decrease high glucose-induced CTGF mRNA and protein expression by 86.4% and 91.8%. PTX could suppress high glucose-induced CTGF expression in mesangial cells. When the PTX dosage increased, the suppressive effect became more remarkable, but PTX had no influence on the TGF-β expression. Conclusions High glucose up-regulates CTGF mRNA and protein expression mainly through TGF-β-Smads pathway. PTX can suppress CTGF expression effectively, but has no direct inhibition of TGF-β expression.