H-2 is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-alpha. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H-2 in endothelial cells. H-2 significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-alpha, at the protein and mRNA levels. The TNF-alpha-induced upregulation of LOX-1 was also attenuated by the NF-kappa B inhibitor N-acetyl-l-cysteine. H-2 inhibited the TNF-alpha-induced activation of NF-kappa B and the phosphorylation of I kappa B-alpha. Furthermore, H-2 inhibited the expression of LOX-1 and the activation of NF-kappa B in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H-2 probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-kappa B activation.