Cerebral ischemia is the commonest cause of death throughout the world. Present investigation deals with the effect of stychedrine on cerebral ischemia induced injury by inhibiting the activity of Histone Deacetylase (HDAC) in neonatal rats. Cerebral ischemia was produced by ligation of carotid artery in neonatal rats. After ligation stachydrine (5 and 10 mg/kg) was given by IP injection in neonatal rats for the period of five days. Infract volume, Apoptosis, HDAC activity, expression of acetylated H3 and H4 proteins, markers of oxidative stress [Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSHPx)] and cytokines were estimated in the cerebral tissues of cerebral ischemic rats. The result suggested that stachydrine treatment significantly (p<0.01) reduced the infract volume, apoptosis ratio, HDAC activity, markers of oxidative stress and cytokines level in the brain tissues of cerebral ischemic neonatal rats compared to negative control group. Moreover it improves the expression of H3 and H4 in the brain tissue of cerebral ischemic neonatal rats. The given study concludes that stachydrine ameliorates the cerebral ischemia in neonatal rats by inhibiting HDAC activity.