Hemodynamic forces have profound effects on vasculature. Laminar shear stress upregulates superoxide dismutase (SOD) expression in endothelial cells. SOD converts superoxide anion to H2O2, which, however, promotes atherosclerosis. Therefore, defense against H2O2 may be crucial in reducing oxidative stress. Since glutathione peroxidase (GPx-1) reduces H2O2 to H2O, the regulation of GPx-1 expression by mechanical stress was examined. Cultured bovine aortic endothelial cells (BAECs) were subjected to laminar shear stress and stretch force. Shear stress upregulated GPx-1 mRNA expression in a time- and force-dependent manner in BAECs, whereas stretch force was without effect. Furthermore, shear stress increased GPx activity. L-NAME, an inhibitor of nitric oxide synthase, did not affect shear stress-induced GPx-1 mRNA expression. The ability of laminar shear stress to induce GPx-1 expression in endothelial cells may be an important mechanism whereby shear stress protects vascular cells against oxidative stress.