In our study, we evaluated the neuroprotective effects of dexmedetomidine on oxidant–antioxidant systems, pro-inflammatory cytokine TNF-α 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 µg/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-α 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 II ( 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-α 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 dexmedetomidine has a neuroprotective effect on hippocampus and dentate gyrus of rats after transient global cerebral I/R injury.