Gentamicin is an aminoglycoside antibiotic that is very effective in treating different gram negative infections, however, one of its main side effects is nephrotoxicity. Gentamicin-induced decreases in glomerular filtration rate could be mediated by mesangial cell contraction. Resveratrol, a natural hydroxystilbene, has been identified to be a potent antioxidant with many biological activities including protection against kidney diseases. As we have previously demonstrated that gentamicin induced a reduction of planar surface area of cultured rat mesangial cells, and that resveratrol has a protective effect on gentamicin-induced nephrotoxicity in vivo, the aim of this study was to investigate the effect of resveratrol on gentamicin-induced mesangial cell contraction. This study demonstrates that the contractile effect of gentamicin on mesangial cells can be prevented by incubation with resveratrol at an optimal dose of 10 microM, as it blunted the gentamicin-induced reduction in planar cell surface area and the number of contracted cells. Besides, the preincubation with 10(-5)M diphenylene iodinium (DPI), an inhibitor of the NADP(H) oxidase, also blunted gentamicin-induced cell contraction. This preventive effect was higher when cells were incubated with both substances together. These results strongly suggest that the protective effect resveratrol against gentamicin-induced reduction in renal function in vivo could be mediated by inhibiting gentamicin-induced mesangial cells contraction.