SummaryThe aim of this study was to test the hypothesis that genistein protects vascular endothelial cells against the pro-atherosclerotic stressor, oxidized low-density lipoprotein (ox-LDL), by inducing antioxidant enzymes and preventing apoptosis. Human umbilical cord-derived endothelial cells (ECV 304) were incubated with genistein (10-100 mol/L), the radical scavenging antioxidant vitamin E ( ␣ -tocopherol, 50 mol/L), or vehicle for 24 h and then were incubated with ox-LDL for an additional 24 h. Subsequently, antioxidant enzyme activities, lipid peroxidation, adhesion to monocytes, cell morphology, viability and apoptotic index were assessed. Ox-LDL decreased superoxide dismutase and glutathione peroxidase activities in endothelial cells and caused lipid peroxidation, adhesion to monocytes, morphological injury and apoptosis ( p Ͻ 0.05). These effects were prevented by vitamin E and dose-dependently by genistein ( p Ͻ 0.05). Further, this effect of genistein is associated with maintenance of antioxidant enzyme activities and inhibition of lipid peroxidation.