OBJECTIVE To investigate the relationship between HIF-1alpha expression and neuron apoptosis in hypoxia/hypoxia ischemia brain injury and elucidate the role of HIF-1alpha in regulating neuron apoptosis. METHODS Postnatal day 10 SD rats were divided into three groups: the hypoxia ischemia group (HI), the hypoxia group and sham controls. Rat brains were collected at 4 h, 8 h and 24 h after hypoxia from each group. Immunohistochemistry was used to detect the protein expression of HIF-1alpha and active caspase-3. Apoptosis positive cells were determined by TUNEL staining. HE staining was used to detect histopathological damage. RESULTS The expression of HIF-1alpha protein was significantly upregulated at 4 h, peaked at 8 h, and decreased at 24 h after hypoxia/HI. The expression level of HIF-1alpha protein in hypoxia/HI group was much higher than that in sham controls (P<0.01). The expression of activated caspase-3 protein was increased at 4 h and 8 h after hypoxia/HI and significantly upregulated at 24 h, but in sham controls the activated caspase-3 protein remains at a very low level (P<0.01). TUNEL staining showed that positive cells significantly increased at 24 h after hypoxia/HI. HE staining showed that neuronal degeneration and edema became prominent at 24 h after hypoxia/HI. The expression of HIF-1alpha protein was higher in hypoxia groups than that in hypoxia ischemia groups at the same time points (P<0.05). However, the expression of activated caspase-3, the number of TUNEL positive cells and the degree of histopathological damage were lower in hypoxia groups than that in hypoxia ischemia groups at the same time points (P<0.05). CONCLUSIONS The variation tendency of HIF-1alpha and activated caspase-3 expression was opposite, and the expression of HIF-1alpha protein and histopathological damage degree was inverse correlation in HIBD. Therefore, it suggested that HIF-1alpha may play a protective role in neuron after hypoxia/HI.