Objective: To study the effect of Lamotrigine on Neuron Specific Enolase(NSE)after hypoxic ischemic brain damage (HIBD) in neonatal rats. Methods: The HIBD models were produced with 7 day old SD rats by subjected to left common carotid artery ligation followed by 3 hrs recovery,then submerged in 37 ℃ water bath with a humidified 8% oxygen 92% nitrogen mixture delivered at 0.5 L/min for 2 hrs. LTG was given 3 hrs after HI at the doses of 10,20 and 40 mg/kg intraperitoneally in group A,and was given at the doses of 20 mg/kg 1hr before and 3,6hrs after HI in group B. Brain and blood were sampled 24h after HI. NSE immunohistochemical method was used for morphological studies. The concentration of NSE in serum was detected by enzyme immunoassay method. Results: In HI groups,NSE levels in the serum were markedly increased when compared with normal controls( P <0.01),and NSE cells could rarely be seen in the left cerebral cortex; In ≥ 20 mg/kg of A groups and all of B groups NSE levels were significantly lower( P <0.01),while the numbers of NSE cells were markedly higher than that in HI group,but still notably lower than that in normal controls. All of the NSE levels and the numbers of NSE cells showed significant statistical difference between the groups of 1h before and 3,6h after HI. Conclusions:Lamotrigine is shown to have neuroprotective effect on HIBD in neonatal rats.