Osthole,a main active constituent from Cnidium monnieri(L.) Cusson,has been considered therapeutic agent in the treatment of ischemic stroke.This study was designed to investigate the effect of osthole on permanent middle cerebral artery occlusion(MCAO) in rats.Osthole was administrated by gavage to the normal and the MCAO rats.Rats were assessed for neurological deficit after 24 h following MCAO,then their brains were evaluated to determine the infarct area,and the mRNA and protein levels of some inflammatory factors were detected.It was found that MCAO animals pre-treated with osthole for 7 d showed significant improvement in all neurological tests compared with vehicle-treated MCAO groups.In addition,there was a significant decrease in infarct volume 24 h after occlusion in animals pre-treated with osthole versus the vehicle-treated MCAO group.MCAO also dramatically caused some inflammatory factors increase.However,pretreatment with osthole restored the mRNA and protein levels of these factors,including TNF-α,IL-1β,COX-2,iNOS of ischemic penumbra cortices,suggesting that osthole possessed the function of preventing brain against ischemic damage,while no significant difference was found in any of normal groups with or without osthole.The present study demonstrated that osthole may be a novel neuroprotective therapy in the treatment of focal ischemic stroke. Osthole, a main active constituent from Cnidium monnieri (L.) Cusson, has been considered a therapeutic agent in the treatment of ischemic stroke. This study was designed to investigate the effect of osthole on permanent middle cerebral artery occlusion (MCAO) in rats. Osthole was administrated by gavage to the normal and the MCAO rats. Rats were assessed for neurological deficit after 24 h following MCAO, then their brains were evaluated to determine the infarct area, and the mRNA and protein levels of some inflammatory factors were detected. It was found that MCAO animals pre-treated with osthole for 7 d showed significant improvement in all neurological tests compared with vehicle-treated MCAO groups. additionally, there was a significant decrease in infarct volume 24 h after occlusion in animals pre-treated with osthole versus the vehicle-treated MCAO group. MCAO also Miming caused some inflammatory factors increase. However, pretreatment with osthole restored the mRNA and protein levels of th ese factors, including TNF-α, IL-1β, COX-2, iNOS of ischemic penumbra cortices, suggesting that osthole possessed the function of preventing brain against ischemic damage, while no significant difference was found in any of normal groups with or without osthole The present study demonstrates that osthole may be a novel neuroprotective therapy in the treatment of focal ischemic stroke.