BACKGROUND: Numerous studies have shown that the increase in self-repair capacity and reproductive activity of brain endogenous neural cells might be an valuable method to treat ischemia-hypoxia brain damage. OBJECTIVE: To study the effects of He-Ne laser irradiation on the proliferation and differentiation of endogenous neural stem cells in newborn rats with hypoxia-ischemia brain damage. DESIGN, TIME AND SETTING: The randomized, controlled study was performed at the College of Nursing, Zhengzhou University from December 2007 to May 2008. MATERIALS: A total of 36 healthy newborn Wistar rats aged 7 days were randomly divided into sham operation, model and laser treatment groups (n = 12). He-Ne laser Therapeutic Equipment with Many Functions were produced by Guilin Electronic Machine Factory, China. METHODS: Newborn rats in the model and laser treatment groups were treated with low-concentration oxygen (containing 8% O2 and 92% N2) following deligation of the left common carotid artery to establish models of ischemia-hypoxia brain damage. Rats in the sham operation group did not receive deligation of the left common carotid artery, but exposed to the air. From the second day of model induction, mice in the laser treatment group were subjected to He-Ne laser irradiation, at 632.8 nm wavelength, 4 mW laser power, 3 mm the diameter of light spot, 56.62 mV power density, 33.975 J/cm2 energy density, 10 minutes once, once a day, 10 days as a course, totally 2 courses, with an interval of 2 days between the two courses. Acupuncture point included Baihui (DU20) on the median parietal bone, and Dazhui (GV14) between the C7 and T1 and the median back. Following treatment, brain hippocampal sections were made and underwent immunohistochemistry for nestin and microtubule-associated protein-2. MAIN OUTCOME MEASURES: Expression of nestin and microtubule-associated protein-2 in rat brain neurons was measured. RESULTS: A total of 36 rats were included in the final analysis. Compared with the sham operation group, nestin expression in the dentate gyrus was significantly increased in the model and laser treatment groups (F=122.36, P < 0.05), and the increased range was greater in the laser treatment group compared with the model group (P < 0.05). Microtubule-associated protein-2 expression was wide in the cerebral cortex, and darkly stained brown dendrite presented radiation-shape. Neurons in the hippocampal pyramid and dentate gyrus granular cell layer arranged regularly. Positively stained dendrite presented branch-shape and distributed in the molecular layer. No significant difference was determined between the sham operation and laser treatment groups. Microtubule-associated protein expression was significantly weakened in the model group. CONCLUSION: He-Ne laser irradiation can promote proliferation of endogenous neural stem cells in neonatal rats with hypoxia-ischemia brain damage, and induce the differentiation into neurons.