Abstract: Objective　To investigate the effects of cordycepin on oxidative stress and expression of caspase-3 and P53 in brain tissue of rats with middle cerebral artery occlusion (MCAO).　Methods　First, rats in the drug-administered group were intraperitoneally injected with 5, 10, and 20 mg/kg of cordycepin for 10 days. Then, the middle cerebral artery occlusion  model was prepared by modified Zea Longa suture method. The neurological function was scored by blind method after the MCAO was prepared for 24h. The brain water content was detected by weighing method. The pathological damage of brain tissue was observed by HE staining and Tunnel staining was used to detect the apoptosis of brain cell. The expression of Bcl-2, Bax, Caspase-3 and p53 mRNA was detected by RT-PCR. The protein expression of Bcl-2, Bax and Caspase were detected by Western blotting. The expression of SOD, MDA, GSH levels were detected by kit.　Results Compared with the MCAO group, the neurological function score, the brain water content, the cell damage and the apoptosis rate of the drug-administered group  significantly reduced. The Bax mRNA and protein expression, the expression of Caspase-3 and p53 mRNA and protein expression significantly down-regulated, and the Bcl-2 mRNA and protein expression significantly up-regulated. The content of MDA decreased, the content of SOD and GSH increased significantly.  With the increasing of cordycepin, the effects were much more effective.　Conclusions　Cordycepin can relieve neurological dysfunction caused by focal cerebral ischemia in the middle cerebral artery and reduce brain water content caused by cerebral ischemia, and can also inhibit apoptosis and oxidative stress in rats with focal cerebral ischemia, which slows the damage caused by focal cerebral ischemia in the middle cerebral artery.

Key words: Cordycepin; ,  , Middle cerebral artery focal cerebral ischemia; ,  ,  Oxidative stress; ,  , Caspase-3; ,  , P53