objective:to investigate the effect of metformin on the proliferation of rat mesangial cells induced by high glucose and the possible mechanism. methods:the rat messangial cells (hbzy-1) were cultured in vitro. ①cultured hbzy-1 cells were divided into four groups:normal glucose(5.6 mmol/l),normal glucose plus metformin(200 mmol/l),high glucose(30 mmol/l),high glucose plus metformin at 50,100,200,400 mmol/l,respectively,and cultured for 6,12,24 h. the proliferation of hbzy-1 cells was detected by micro-tetrazolium salt colorimetric enzyme reaction test(mtt). ②cultured hbzy-1 cells were divided into four groups:normal glucose(5.6 mmol/l),normal glucose plus metformin(200 mmol/l),high glucose(30 mmol/l),high glucose plus metformin(200 mmol/l),and cultured for 12 h. the protein levels of tgf-β1,p-ampk and ampk were measured by western blot. results:as compared to normal cells,exposure of hbzy-1 cells to d-glucose at concentration of 30 nmol/l caused a time-dependent increase in the proliferation of hbzy-1 cells and reached the highest level at approximately 12 h. the addition of metformin significantly attenuated the high glucose-enhanced proliferation of hbzy-1 cells (p < 0.01) in a dose-dependent manner. but no notable difference was found between normal glucose plus metformin group and normal glucose group(p > 0.05). as compared to normal cells,the levels of tgf-β1 protein significantly increased,and the levels of p-ampk significantly decreased in high glucose group(p < 0.01). metformin significantly attenuated the increase of tgf-β1 expression and increased the expression of p-ampk in hbzy-1 cells exposured to high d-glucose(p < 0.01). conclusion:high glucose contributes to an increased proliferation of hbzy-1 cells. metformin can significantly reverse high glucose up-regulated proliferation of hbzy-1 cells through inhibiting the expression of tgf-β1 protein and increasing the expression of p-ampk protein in hbzy-1 cells.