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A neonatal rat model of hypoxic-ischemic brain damage was designed and implemented in this study.Rats were subjected to hypothermia at 31°C immediately follow ing hypoxia-ischemia for either 3, 6 or 15 hours.TdT-mediated dUTP nick end labeling demonstrated that the number of apoptotic cells was reduced in the rat cerebral cortex, hippocampus and periventricular white matter following hypothermia.Immunohistochemistry revealed that Bcl-2 and p16 expression were decreased.Inhibition of apoptosis was greatest with the 3 hour hypothermic treatment, followed by hypothermia for 6 hours.In contrast, hypothermia for 15 hours led to a decrease in neuronal number in the cerebral cortex.The results demonstrate that hypothermic intervention at 31°C protects brain tissue against hypoxic-ischemic brain damage by inhibiting apoptosis, and that the optimal length of treatment is 3 hours.