Acute lung injury (ALI) is a common cause of respiratory failure in critically ill patients with a mortality rate of 38.5%. ALI can be precipitated by either direct insults such as pneumonia, aspiration or via indirect insults such as sepsis and multiple trauma, to the lungs. The vascular endothelium forming the innermost lining of all pulmonary blood vessels is the major barrier that protects air spaces against vascular fluid entry. Because of their localization, endothelial cells (EC) are constantly exposed to oxygen and nutrients that fuel cell metabolism. However, very little is known about the role of EC metabolism in the regulation of EC inflammation and permeability, the two major pathogenic features of ALI. Recent studies have highlighted that fatty acid oxidation (FAO) is central to the tight regulation of EC permeability required to maintain vessel functionality. The purpose of the present study is to understand the mechanistic link between cell metabolism and thrombin‐induced EC inflammation and permeability and to understand the relevance of this linkage in the pathophysiology of ALI. Human Pulmonary Artery Endothelial cells (HPAECs) were stimulated with proinflammatory mediator thrombin in the presence and absence of Etomoxir, an inhibitor of FAO or dichloroacetate (DCA), an inhibitor of pyruvate hydrogenase kinase (PHK). Our results indicate that both Etomoxir and DCA inhibited thrombin‐induced inflammatory responses as observed by decrease in the secretion of cytokines IL‐6 and IL‐8. In addition real time changes in transendothelial electrical resistance (TER) were measured to monitor endothelial permeability after exposure of HPAECs to Etomoxir or DCA, followed by thrombin treatment. Our data indicate that Etomoxir had no effect on thrombin‐induced decrease in TER however it delayed the recovery after 1 hour of thrombin challenge. DCA in contrast showed no effect on thrombin‐induced EC permeability. Together our data suggest that metabolic pathways are critical to EC inflammation and permeability induced by thrombin.Support or Funding InformationSupported by: NIH (HL130870)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.