Objective To investigate the role of protease activated receptor-1 and 4 (PAR-1, PAR-4) in the activation of microglia following subarachnoid hemorrhage (SAH). Methods One hundred male SD rats were randomly divided into: sham, SAH+control siRNA, SAH+PAR-1 siRNA, SAH+PAR-4 siRNA and SAH+PAR-1/4 siRNA groups, 20 in each group. The drugs were administrated intracerebroventricularly at 1 hour after SAH. At the 6th and 24th hour after SAH, the neurological deficits, brain water content and Evans blue content were evaluated, at the same time, the expression of tumor necrosis factor α(TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were also measured by using immunohistochemistry and Western blotting. Results PAR-1siRNA or PAR-4 siRNA could significantly ameliorate the neurological deficits and decrease vascular permeability (EM>P/EM>0.05). In addition, the expression of TNF-α and ICAM-1 was also decreased by PAR-1siRNA or PAR-4 siRNA treatment. The combination of PAR-1and PAR-4 siRNA played more powerful roles than either of them. Conclusion PAR-1 and 4 mediate the activation of microglia in the brain following SAH. Through suppressing the expression of inflammatory factors, PAR-1siRNA and/or PAR-4 s