Abstract:  Skin is the first barrier preventing microorganism invasion in host. Wounds destroy this defense barrier and, without an appropriate care, may lead to sepsis. Neutrophil activation and immigration plays an important role at the inflammatory stage of wound healing. Neutrophils are known to express proteinase‐activated receptors (PARs), which can be activated by serine proteases, also by enzymes involved in wound healing. We previously reported that PAR₂ agonists up‐regulate cell adhesion molecule expression and cytokine production by human neutrophils. Here, we demonstrate that PAR₂ agonists (serine proteases as well as synthetic peptides) reduce transendothelial migration of neutrophils and prolong their life in vitro. Synthetic PAR₂ agonist also enhanced protective interferon (IFN)γ‐induced FcγRI expression at neutrophil cell surface. Of note, IFNγ is a cytokine, which was used in clinical trials to reactivate human neutrophil functions during sepsis. Moreover, we observed a significant increase of PAR₂ expression on cell surface of neutrophils from septic patients as compared with healthy volunteers. Together, our results indicate that PAR₂ may be involved in the pathophysiology of neutrophil‐endothelial interactions during wound healing or later during sepsis in humans, potentially by affecting neutrophil apoptosis, transendothelial migration and Fcγ receptor‐mediated phagocytosis.