Abstract Injury or dysfunction of the vascular endothelium is one of the first events in the development of atherosclerosis. Individual lipids, e.g. fatty acids or lipoproteins, are among the most critical factors which may induce injury to the endothelium. Selected fatty acids, such as linoleic acid, can disrupt endothelial barrier function and increase the inflammatory response of the vascular endothelium. The mechanisms of these processes are not fully understood. It is hypothesized that selected fatty acids can mediate the autocrine production of tumor necrosis factor-α in endothelial cells. This will activate a variety of intracellular signaling pathways and further potentiate endothelial injury initially induced by fatty acids.