In this proof-of-principle study, we could show for the first time that VT, a novel PEG-clustered synthetic 7-mer reported to activate Tie2 in endothelial cell culture and to promote angiogenesis in experimental diabetic ulcers, augments Tie2 activation in vivo and effectively protects against sepsis-induced vascular leakage and leukocyte transmigration in a clinically relevant murine model of polymicrobial abdominal sepsis. Here, TEK is linked to Sepsis.