Inflammatory processes of vascular endothelial cells play a key role in the development ofatherosclerosis. We determined the anti-inflammatory effects and mechanisms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on LPS-treated human umbilical vein endothelial cells (HUVECs) to evaluate their cardioprotective potential. Cells were pretreated with DHA, EPA, or troglitazone prior to activation with LPS. Expression of COX-2, prostaglandin E2 (PGE2) and IL-6 production, and NF-ՊB activity were measured by Western blot, ELISA, and luciferase activity, respectively. Results showed that EPA, DHA, or troglitazone significantly reduced COX-2 expression, NF-ՊB luciferase activity, and PGE2 and IL-6 production in a dose-dependent fashion. Interestingly, low doses (10ՌM) of DHA and EPA, but not troglitozone, significantly increased the activity of NF-ՊB in resting HUVECs. Our study suggests that while DHA, EPA, and troglitazone may be protective on HUVECs under inflammatory conditions in a dose-dependent manner. However there may be some negative effects when the concentrations are abnormally low, even in normal endothelium.