beta-Sitosterol, normally present in vegetable-containing diets, comprises an important component of cholesterol controlling functional foods. It has been associated with cardiovascular protection, exerting its effect mainly through increasing the antioxidant defense system and effectively lowering the serum cholesterol levels in humans. However, its anti-inflammatory effect on endothelium is unknown. Attachment of leukocytes to the vascular endothelium and the subsequent migration of cells into the vessel wall are early events in atherogenesis, this process requiring the expression of endothelial adhesion molecules. We examined the effect of beta-sitosterol (0.1-200 microM) on (i) the expression of vascular adhesion molecule 1 and intracellular adhesion molecule 1 by cell ELISA and (ii) the attachment of monocytes (U937 cells) in tumor necrosis factor-alpha (TNF-alpha)-stimulated human aortic endothelial cells (HAECs) by adhesion assay. The effect on nuclear factor-kB phosphorylation was also examined via a cell-based ELISA kit. Results showed that beta-sitosterol inhibits significantly vascular adhesion molecule 1 and intracellular adhesion molecule 1 expression in TNF-alpha-stimulated HAEC as well as the binding of U937 cells to TNF-alpha-stimulated HAEC and attenuates the phosphorylation of nuclear factor-kB p65. This study extends existing data regarding the cardioprotective effect of beta-sitosterol and provides new insights into understanding the molecular mechanism underlying the beneficial effect of beta-sitosterol on endothelial function.