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Activation of the coagulation cascade is commonly observed in the lungs of patients with both acute and chronic inflammatory and fibrotic lung disorders, as well as in animal models of these disorders. The aim of this study was to examine the contribution of the major thrombin receptor, proteinase-activated receptor-1 (PAR-1), during the acute inflammatory and chronic fibrotic phases of lung injury induced by intratracheal instillation of bleomycin in mice. Inflammatory cell recruitment and increases in bronchoalveolar lavage fluid (BALF) protein were attenuated by 56 ± 10% (P < 0.05) and 53 ± 12% (P < 0.05), respectively, in PAR-1-deficient (PAR-1^−/−) mice compared with wild-type (WT) mice. PAR-1^−/− mice were also protected from bleomycin-induced pulmonary fibrosis with total lung collagen accumulation reduced by 59 ± 5% (P < 0.05). The protection afforded by PAR-1 deficiency was accompanied by …