Abstract: This study is to investigate the effects of paeoniflorin on cerebral blood flow and the balance of PGI₂/TXA₂ of rats with focal cerebral ischemia-reperfusion injury. A total of 72 SD rats (♂) were randomly divided into 6 groups: sham operation group, cerebral ischemia-reperfusion model group (I/R gourp), low (10 mg·kg^-1), middle (20 mg·kg^-1) and high (40 mg·kg^-1) doses of paeoniflorin groups and nimodipine group. Focal cerebral ischemia in rats was made by inserting a monofilament suture into internal carotid artery for 90 min and then reperfused for 24 h. The effects of paeoniflorin on neurological deficit scores and the infarction volume of brain were detected. Relative regional cerebral blood flow (rCBF) was continuously monitored over ischemic hemispheres by laser-Doppler flowmetry (LDF). The expression of COX-2 in hippocampal CA1 region was estimated by immunohistochemistry and the contents of prostacyclin I₂ (PGI₂), thromboxane A₂ (TXA₂), and ratio of PGI₂/TXA₂ in serum were measured by ELISA kits. Paeoniflorin significantly ameliorated neurological scores, reduced the infarction volume, and increased regional cerebral blood flow relative to the I/R group. In addition, paeoniflorin could inhibit COX-2 expression and the release of TXA₂ and prevent the down-regulation of PGI₂ induced by I/R injury. The neuroprotective effects of paeoniflorin against focal cerebral ischemia-reperfusion rats might be attributed to improve the supply of injured hemisphere blood flow and adjust the balance between PGI₂/TXA₂.