The aim of the present research was to determine the effect of punarnavine against global cerebral ischaemic injury in mice. Occlusion of bilateral common carotid artery of control and drug treated mice for 20 min followed by 1-h reperfusion resulted in marked disorganization and ischaemic necrosis in pyramidal cells of the brain tissue. Twenty-four and 48 h after reperfusion, the neurocyte survival rate decreased and apoptosis rate increased. Moreover, significant increase in Thiobarbituric acid reactive substance (TBARS) and significant decrease in the reduced glutathione (GSH) levels was seen in the brain tissue. All the above mentioned findings were significantly reduced/ reversed in the animal groups treated with punarnavine in a dose dependant manner. The results indicate a positive protective effect of punarnavine in the ischaemic neuronal injury and associated pathological conditions like stroke.