This study is dedicated to the research of the regulatory peptide PGP and its acetylated form (N-AcPGP) effect on the paw edema formation and vascular permeability in rat skin. Edema was induced by subcutaneous administration of histamine. Vascular permeability was determined by intradermal injection of mast cells activators corticotropin-releasing hormone (CRH), lipopoly-saccharide (LPS), Synacthen (corticotropin analogue), histamine and compound 48/80. We established that PGP reduced the size of the paw edema, but N-AcPGP had an opposite effect increasing paw edema. Skin vascular permeability didn't increase in rats under the administration of PGP or N-AcPGP with additional injections of CRH, LPS and Synacthen, but with additional injections of histamine and substance 48/80. We demonstrated in vitro that pretreatment with both PGP and N-AcPGP reduced histamine secretion by rat's peritoneal mast cells under activation by Synacthen. These results provide evidence that the effect of the peptides on vascular permeability is mainly mediated by the influence on the secretory activity of mast cells.