OBJECTIVE To investigate the roles of protease-activated receptors (PARs) in thrombin-induced brain injury and neurogenesis in rats. METHODS Ninety male SD rats were randomly assigned to receive intra-hippocampus injection of NS, thrombin or specific agonists of 3 protease-activated receptors (PAR-1, PAR-3 and PAR-4), respectively. At 1,3 and 7 d after injection, the area of the hippocampus was determined with HE staining, the density and morphology of astrocyte were detected with GFAP staining, degenerated neurons were detected with Fluoro-Jade C staining, and the neurogenesis was examined with DCX staining. RESULTS Compared to NS injection, the area of the hippocampus significantly increased at 1-3 d and decreased at 7 d after the injection of thrombin and PAR-1 agonist (P<0.05). In addition, injection of thrombin and PAR-1 agonist significantly increased the density of astrocyte and Fluoro-Jade C positive cells at 1-7 d after injection (P<0.05), and significantly increased the density of DCX positive cells at 3-7 d after injection(P<0.05). The injection of PAR-3 agonist and PAR-4 agonist had no affect on the area of the hippocampus, the density of astrocyte, Fluoro-Jade C positive cells and DCX positive cells. CONCLUSION The activation of protease-activated receptor-1 may be related to the thrombin-induced brain injury and neurogenesis in rat hippocampus.