The transcriptional regulatory protein nuclear factor kappa B (NF-κB) participates in the control of gene expression of many modulators of inflammatory and immune responses, including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The heightened expression of these adhesion molecules has been reported to play a critical role in atherosclerosis, inflammation, ischemic vascular disorders, diabetes, and cancer metastasis. In the present study, we investigated the effect of pycnogenol, an antioxidant phytochemical, on the activation of NF-κB and the induction of VCAM-1 and ICAM-1 in tumor necrosis factor (TNF)-α-treated human umbilical vein endothelial cells (HUVECs). Gel-shift analysis of HUVEC demonstrated that pretreatment with pycnogenol exhibited a concentration-dependent suppression of TNF-α-induced activation of NF-κB. Induction of VCAM-1 and ICAM-1 surface expression by TNF-α was dose-dependently reduced by pycnogenol. TNF-α significantly increased the release of superoxide anion and hydrogen peroxide from HUVECs. Pycnogenol dose-dependently inhibited their release. The ability of pycnogenol to inhibit NF-κB activation and VCAM-1 and ICAM-1 expression suggests that this phytochemical may play an important role in halting or preventing the atherogenic process.