To investigate the effect of vitamin E on the proliferation activity of vascular smooth muscle cells (SMCs) in diabetes mellitus, [3H]-thymidine incorporation was measured in cultured SMCs isolated from normal and streptozotocin-induced diabetic rats treated with or without vitamin E and/or allylamine. Untreated diabetic rats demonstrated significantly elevated concentrations of serum total cholesterol, triglycerides and malondialdehyde (MDA). Allylamine caused a further increase in serum MDA. Treatment with vitamin E decreased the serum concentrations of triglycerides and MDA in both allylamine-treated and -untreated diabetic rats. [3H]-Thymidine incorporation in cultured SMCs from diabetic rats was significantly increased compared with that from normal rats. SMCs from allylamine-treated diabetic rats showed an enhanced increase in thymidine incorporation compared with that from untreated diabetic rats. The increase in thymidine incorporation in SMCs from untreated and allylamine-treated diabetic rats was significantly reduced by the treatment with vitamin E. These observations suggest that vitamin E has a preventive effect on the proliferation of vascular SMCs in diabetes, and that this effect may be mediated through an enhancement of free radical scavenging.