Eugenol, a natural constituent of a number of aromatic plants and their essential oil fractions, has several biological effects. However, its protective effects against endothelial injury remain unclarified. This study investigates how eugenol affects human umbilical vein endothelial cells (HUVECs) dysfunction mediated by oxidized low density lipoprotein (oxLDL). Our results showed that the suppression of endothelial NO synthase (eNOS) expression, enhancement of adhesion molecules (ICAM, VCAM, and E-selectin) expression, and adherence of monocytic THP1 cells caused by a non-cytotoxic concentration (100 microg/ml) of oxLDL were ameliorated following a eugenol treatment (12.5-100 microM) in HUVECs. Eugneol also inhibited the reactive oxygen species (ROS) generation, intracellular calcium accumulation, and the subsequent mitochondrial membrane potential collapse, cytochrome c release and caspase-3 activation induced by oxLDL. The cytotoxicity and apoptotic features induced by a cytotoxic concentration (200 microg/ml) of oxLDL was also attenuated by eugenol. Our results suggest that eugenol may protect against the oxLDL-induced dysfunction in endothelial cells.