Cerebral ischaemia reperfusion (I/R) triggers a complex series of biochemical events that lead to formation of reactive oxygen species (ROS) and the impairment of enzymatic mechanisms, which result in tissue oxidative stress. This study investigated the effect of some neuroprotective drugs such as vinpocetine, cinnarizine, pyritinol, and rosiglitazone on oxidative stress and cell death biomarkers occurred during experimental brain ischemia/reperfusion injury in rats. Adult male albino Wistar rats were subjected to 1 hr of brain ischaemia followed by reperfusion for 2 hr. Rats were orally treated with aqueous suspension of vinpocetine (3 mg/kg), cinnarizine (7 mg/kg), pyritinol (55 mg/kg), and rosiglitazone (0.5 mg/kg), after 1 hr of ischaemia. Brain superoxide dismutase (SOD), glutathione (GSH), and malondialdhyde (MDA) contents and serum nitric oxide (NO), lactate dehydrogenase (LDH), catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PDH) levels were quantified at the end of the experiment. I/R injury caused a significant decrease in the activity of brain SOD, GSH contents and serum CAT level. It caused a significant increase in serum NO, LDH, G6PDH levels, and brain MDA content in comparison with the sham-operated group. Vinpocetine and rosiglitazone reversed all these biochemical indices. Pyritinol reversed all these biochemical indices except serum NO, and G6PDH. Cinnarizine could not affect brain MDA, serum NO and CAT levels. Both vinpocetine and rosiglitazone may be potent neuroprotective agents against experimental brain I/R injury in rats. Cinnarzine and pyritinol showed a marked neuroprotective activity but less than both drugs.