High glucose and elevated levels of advanced glycosylation end products (AGEs) exert an antiproliferative effect on cultured mesangial cells. In view of the role of oxygen free radicals in the pathogenesis of diabetic nephropathy, we tested whether two endogenous antioxidants, taurine and vitamin E, ameliorate the effects of an elevated ambient glucose and/or AGEs on mesangial cell growth in vitro. Regardless of whether cell proliferation was assayed by the incorporation of [3H]thymidine, direct cell counting or bromodeoxyuridine (BrdU) cell staining, both taurine and vitamin E reversed the inhibitory effect of high glucose and AGEs on mesangial cell growth. In conjunction with our previous studies indicating that taurine and vitamin E reduce collagen production in mesangial cells exposed to high glucose, these findings suggest that endogenous antioxidants attenuate diabetic glomerulosclerosis by interfering with the bioactivation of transforming growth factor-6.