Objective: To investigate the effects of moxibustion on the behavioral performance, brain morphological structure of mice with hypoxia-ischemia brain injury and to explore its mechanisms. Methods: One hundred and six ICR mice were randomly divided into three groups, sham group (n=23), model group (n=46) and moxibustion-treated group (n=37). Neonatal hypoxic-ischemia brain injury was induced by ligation of common carotid artery followed by hypoxia (8% oxygen, 100 min), and pups in the moxibustion-treated group were administered suspended moxibustion on the Dazhui points (GV14) at a height of approximately 2 cm over a hairless area of the skin once a day for 4 days (i.e. at 2, 24, 48 and 72 hours after hypoxia-ischemia procedure). Behavioral tests were used to evaluate behavioral performance. HE staining was used to observe brain morphological structure. Western blot was used to detect the expression of SOD2 protein, and spectrophotometry was used to determine the content of MDA in the ipsilateral brain. Results: Mouse pups in sham group showed that the behavioral performance was normal, the brain tissue cells were densely and neatly arranged, the expression of SOD2 and the level of MDA in the brain tissues were normal. Compared with sham group, mouse pups in the HI model group exhibited a significant longer latency to complete the righting reflex, geotaxis reflex, cliff avoidance (P＜0.05) and a marked shorter latency to complete the grip test (P＜0.05); and the HI model group had dramatic brain morphological changes showing missing regions, decreased expression of SOD2 protein (P＜0.05) and increased level of MDA in the brain. Compared with HI model group, mouse pups in the moxibustion-treated group exhibited a significant shorter latency to complete the righting reflex, geotaxis reflex, cliff avoidance test (P＜0.05) and a marked longer latency to complete the grip test (P＜0.05); and the moxibustion-treated group had less brain morphological changes, increased expression of SOD2 protein (P＜0.05) and decreased level of MDA in the brain (P＜0.05) . Conclusion: Moxibustion could improve behavioral performance and attenuate hypoxia-ischemia brain injury, which might be related to increasing the expression of SOD2 protein and decreasing the content of MDA, thus enhancing the anti-oxidative ability.