Protease-activated receptor 2 (PAR-2) is involved in inflammatory, gastrointestinal, and vascular diseases. The aim of the present work was to elucidate the minimal structural features for PAR-2 agonist activity in short peptides. Our study resulted in the discovery of dipeptide derivatives of N(alpha)-benzoyl-Arg(NO(2))-Leu-NH(2) displaying a potency comparable to that of the full-length rat PAR-2 activating peptide (Ser-Leu-Ile-Gly-Arg-Leu-NH(2)).