In our study, we evaluated the neuroprotective effects of dexmedetomidine on oxidantantioxidant systems, pro -inflammatory cytokine TNF-a and number of apoptotic neurons on hippocampus and dentate gyrus after transient global cerebral I/R injury. Eighteen rats divided into 3 groups, equally. Group I rats were used as shams. For group II and III rats, they were prepared for transient global cerebral ischemia using a four-vessel- occlusion model. 5 mL/kg/h 0.9% sodium chloride was infused to the Group II and 3 Pg/kg/h/5 ml dexmedetomidine was infused to the Group III for 2 h after I/R injury. The levels of MDA and NO and activities of SOD and CAT were measured in the left hippocampus tissue. The levels of TNF-a concentration were measured in the plasma. The number of apoptotic neurons was counted by TUNNEL method in histological samples of right hippocampus tissue. MDA and NO levels increased in Group II compared with Group I rats (p=0.002, p=0.002, respectively). In group III, MDA and NO levels decreased as compared to Group 11 (p=0.015, p=0.002, respectively). SOD and CAT activities increased in Group III as compared to Group II rats (p = 0.002, p = 0.002, respectively). The decrease in TNF-a levels of group III was significant as compared to group II (p=0.016). The number of apoptotic neurons in group III was lower than Group II rats. Our study showed that dexinedetomidine has a neuroprotective effect on hippocampus and dentate gyrus of rats after transient global cerebral I/R injury. (c) 2008 Elsevier B.V. All rights reserved.