Background: Hypoxic-ischemic brain damage (HIBD) that often results in cerebral palsy continues to be a common disease in perinatal medicine. At present, no effective therapeutic strategies has yet been developed to counteract this condition. Objective: To study the effect of He-Ne laser acupoint irradiation and electric acupuncture on hippocampal neuron survival and development as well as the expressions of brain-derived neurotrophic factor(BDNF) and choline acetyl transferase(ChAT) in HIBD in neonatal rats. To compare and analysis the different effectiveness of two treatments in order to explore the new method against HIBD. Design: A completely randomized controlled study. Setting and participants: The study was conducted at the Department of Anatomy of the Second Military Medical University of Chinese PLA and Zhengzhou University. Fifty-eight seven-day-old rats were obtained from the experimental animal center of Henan Province with a body mass from 12 to 15 g in either gender. Interventions: Rats were randomly allocated into four groups: control group(I) that neither ligated nor exposed to hypoxia, HIBD group(II) that exposed to hypoxic-ischemic condition, laser irradiation group(III) and electric acupuncture group(EA, IV). Left brain Hypoxic-ischemic injury model were established in all animals of II-IV groups on basis of Yu Xiaohong's animal model of unilateral hypoxia-ischemia in neonatal rats. Animals in group III and IV were treated either with He-Ne laser acupoint irradiation(III) or EA(IV) in the next day following hypoxia synchronously by choosing dazhui and baihui acupoints for the treatment. Fifty-eight rats were subjected to perfusion-fixation 22 days later, the left brains were paraffin wax embedded, sectioned and stained by HE and Nissl staining as well as ChAT and BDNF immunohistochemical staining. Main outcome measures: The neurons and Nissl bodies were observed, the grey scale values were measured and the number of ChAT and BDNF positive neurons was counted under microscope. Data were statistically analyzed. Results: 1 The structure of neurons in hippocampus and cortex was clear in group I, and the neuronal cytoplasm was full of dark-blue-colored Nissl bodies(grey scale value was 122.90 ± 12.10); there were neuron degeneration and necrosis in group II, a great number of Nissl bodies in surviving neurons were lost(grey scale value was 188.31 ± 10.43); The neuron degeneration, necrosis and the loss of Nissl bodies reduced in laser III or EA IV and grey scale value decreased respectively (130.56 ± 6.16 and 135.19 ± 7.00); 2 The number of ChAT and BDNF positive neurons was 29.74 ± 4.85 and 13.42 ± 5.56 respectively in hippocampus in group I; ChAT positive neurons decreased 13.96 ± 7.62 and BDNF positive neurons heightened 21.93 ± 5.12 in group II; ChAT and BDNF positive neurons all increased significantly to 26.42 ± 6.02 and 33.02 ± 7.58 in hippocampus respectively in group III; ChAT and BDNF positive neurons also increased to 25.54 ± 5.05 and 27.63 ± 7.15 respectively in group IV; 3 There were significant differences in grey scale and the number of positive neurons between control and each treatment group(P < 0.05); The variation in group III was more obvious than that of group IV. Conclusion: He-Ne laser acupoint irradiation and EA have neuroprotective effects against hypoxic ischemia, which can promote the survival, development and function of hippocampal neurons. The impact of He-Ne laser acupoint irradiating is more significant than EA. The mechanism of the difference between the effectiveness of these two treatments still requires further validation, although it can be presumed that He-Ne laser not only has biological function as EA but also can improve some restoring enzymes of injured neurons.