The present study was designed to examine whether the methanol extract of Sorbus commixta cortex (MSC) could prevent the development of atherosclerosis through regulating the vascular nitric oxide (NO) and endothelin-1 (ET-1) systems in atherogenic-diet rats. Our findings show that aortic NO production as well as endothelial nitric oxide synthase (ecNOS) expression was significantly decreased in atherogenic-diet rats compared with those in the control group. Aortic ET-1 expression was augmented in rats fed an atherogenic-diet while NF-kappaB p65 was upregulated. Treatment of atherogenic-diet rats with either low (100 mg/kg/d) or high (200 mg/kg/d) doses of MSC led not only to significant increases in the aortic NOS/NO system, but also to decreases in aortic ET-1 expression. The aortic expression level of NF-kappaB p65 was also attenuated in atherogenic-diet rats by chronic treatment with low or high doses of MSC. Atherogenic-diet induced increases in the expression of adhesion molecules including intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were markedly decreased by treatment with MSC. From the histopathological examination, MSC treatment was shown to lessen the thickening noted in the aortic intima and media of the atherogenic-diet rats. These results suggest that MSC affects the atherogenic process via the suppression of proinflammatory and adhesion molecules in atherogenic-diet rats, which may be, at least in part, causally related with the regulation of vasoactive systems such as the NO and ET-1 systems.