Endothelial injury can be the cause and consequence of severe inflammation and injury. Synthetic somatostatin analogs-which suppress Growth Hormone-are clinically-approved drugs associated with anti-inflammatory activities. In the present study, we suggest that the protective activities of Octreotide in human and bovine endothelial cells are mitigated by Ceapin-A7, which is an activating transcription factor 6 inhibitor. To study endothelial function, we assessed protein expression levels of key cytoskeletal proteins, as well as paracellular permeability. To evaluate inflammation, we measured factors that promote vascular leak, as well as reactive oxygen species generation. Collectively, our study supports the involvement of activating transcription factor 6 in the protective effects of Octreotide in endothelial barrier function.