The ideal treatment for diabetic nephropathy should slow the progress of renal failure, delay the initiation of dialysis, and protect residual renal function in patients receiving dialysis. Renal mesangial cells play an important role in these processes. In the current study, we investigated the effects of genistein on rodent renal mesangial cells cultured in a high-glucose environment. Since overexpression of the extracellular matrix (ECM) components (type IV collagen and fibronectin) and transforming growth factor beta (TGF-beta) have been previously implicated in the development of the renal glomerulus damage of diabetic nephropathy, we included these substances in our study. The results showed that high concentration of glucose (450 mg.dl(-1)) stimulated the synthesis of type IV collagen and fibronectin and the secretion of TGF-beta. These responses were attenuated by genistein (> or =5 micromol.l(-1)) in a dose- and time-dependent manner. In conclusion, we demonstrated that genistein could inhibit the secretion of ECM components and the expression of TGF-beta at both the protein and mRNA levels. These findings should be followed up by further studies and clinical trials to verify the potential therapeutic effects of genistein on diabetic nephropathy.