OBJECTIVE: The study was to investigate the effect of different temperatures during hypoxia on brain injury in mice of different ages. METHODS: Newborn C57/BL6 mice at 7 days or 21 days of life were subjected to left carotid artery ligation followed by exposure with 10% oxygen. The mice were kept in a incubator with a predetermined, constant temperature, either 34℃ (Hypothermia group) or 36℃ (Normothermia group). Brain injury was evaluated 7 days after hypoxia-ischemia (HI). Active caspase-3 and apoptosis-inducing factor (AIF) expressions in the brain tissue were detected by immunohistochemistry and Western Blot was used to evaluate the phosphor-Akt (P-Akt) expression in the brain tissue at 24 hrs post-HI. RESULTS: Brain injuries, including the cortex, hippocampus, striatum and thalamus injuries, occurred in the Normothermia group at 7 days post-HI. The brain cortex showed cystic cavitation in the postnatal day (P)7 pups mice and laminar infarct of the brain cortex was observed in P21 mice. In the Hypothermia group, the P7 mice did not present with laminar infarct of the cortex and had lower scores of neuropathological lesions in cortex, hippocampus, striatum and thalamus than P7 mice from the Normothermia group (P<0.01); the cortex injuries were significantly relieved but the injuries of hippocampus, striatum and thalamus in P21 mice were similar to those from the Normothermia group. Active caspase-3 (7.0±5.6)and AIF positive cells (3.7±6.2) in the cortex of P7 mice from the Hypothermia group were significantly lower than those of the Normothermia group (51.5±23.2 and 31.8±22.4) at 24 hrs post-HI (P<0.01). Wetstern Blot showed the P-Akt expression was obviously decreased in the ipsilateral hemisphere to the occlusion compared with that of the contralateral hemisphere after HI in the Normothermia group (P<0.05), while in the Hypothermia group the P-Akt expression was not significantly different between the two hemispheres. CONCLUSIONS: Hypothermia has protective effects against HI insults. The protection was more pronounced for the immature brain than the mature brain.