Endothelial cells form a thin cell layer at the inner wall of vessels that line the entire circulatory system. They act as a selective barrier between vessel lumen and the surrounding tissue. Dysfunction of this barrier is involved in various diseases such as inflammation or atherosclerosis. Prostaglandin E2 (PGE2) plays a crucial role during immune responses including fever, pain and tumorigenesis. During an immune response, inflammatory cells, fibroblasts and the epithelium are the main source of PGE2.The aim of my study was to investigate the influence of PGE2 and its receptor, EP4, on the endothelial barrier function. To this end, EP4 receptor of human microvascular endothelial cells of the lung was silenced via RNA interference and shown on mRNA and protein levels. Additionally, the functional impact of EP4 receptor silencing was observed by measuring electrical impedance of endothelial monolayers. Here, silencing of EP4 receptor resulted in a decreased barrier enhancement in response to PGE2 and the EP4 selective agonist ONO AE1-329. The EP4 receptor-induced morphological changes of cell-cell junctions were visualized by fluorescence microscopy. Thrombin-induced disruption of the endothelial monolayer resulting in disorganization could be prevented by pretreatment with PGE2 and the selective EP4 agonist. Furthermore, the impact of the EP4 receptor on endothelial cell cycle and apoptosis was considered. While activation of EP4 receptor did not promote the cell cycle, pretreatment with PGE2 and the EP4 agonist showed protective effects upon staurosporine-induced apoptosis.Taken together, these data suggest the EP4 receptor as a potential target for treating diseases with increased vascular permeability such as acute lung injury. Activation of this receptor stimulates so far not yet fully understood downstream signaling that enhances the endothelial barrier. Therefore, this finding provides a good basis for further investigation of possible signaling pathways.