Functions of thrombin as a modulator of inflammation and tissue repair are mediated by the proteinase-activated receptor (PAR) family. Some of these effects may be induced by activation of mast cells. To characterize the degranulation of rat peritoneal mast cells in response to PAR agonists, the effects of thrombin, trypsin and peptide agonists of PARs (PAR-AP, proteinase-activated receptor-activating peptides) on secretion were investigated. The release of β-hexosaminidase by thrombin (0.01–1 μM) was concentration-dependent and mediated via PAR 1, as evidenced by cathepsin G (100 μM)-induced inactivation of PAR 1 and thrombin-stimulated PAR 1 desensitization. Trypsin (1 μM) accelerated histamine secretion. The PAR 1-AP, TRAP (SFFLRN, 1–100 μM) and the PAR 2-AP SLIGRL (5–100 μM) caused the release of histamine, and β-hexosaminidase from inflammatory mast cells were obtained from a model of acute peritonitis in rats. Relative to the response to compound 48/80, the thrombin- and TRAP-induced release of β-hexosaminidase was higher in inflammatory mast cells than in the control. This suggests that additional exposure of PAR 1 on mast cells to PAR agonists or an increase in PARs sensitivity to PAR agonists probably occurred during acute inflammation.