OBJECTIVE: It was aimed to study the expression of redoxfactor-1 (APE/Ref-1) protein in the cerebral tissues of neonatal rats after hypoxic-ischemic brain damage (HIBD) and its relationship to apoptosis. METHODS: Seven-day-old neonatal rats were randomly assigned into a Normal control group, a Sham-operation group and a Hypoxic-ischemic (HI) group. The HIBD model was established through the ligation of left common carotid artery along with hypoxic exposure. The expression of APE/Ref-1 protein and apoptosis were determined by immunohistochemistry and terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) staining at 1, 3, 6, 12, 24 and 48 hrs after HI. RESULTS: Immunohistochemistry results showed extensive nuclear expressions of APE/Ref-1 in the Normal control and Sham-operation groups, and there was no significant difference between the two groups. In the HI group, the nuclear expression of APE/Ref-1 protein decreased significantly with the HI time. The APE/Ref-1 protein expression in the cerebral cortex was significantly different at different HI time points. In contrast, apoptotic cells increased with the HI time and reached a peak 24 hrs after HI. Significant differences were observed in both the APE/Ref-1 protein expression and the number of apoptotic cells between the HI group and the Normal group as well as the Sham-operation group. CONCLUSIONS: The results suggested that the reduction of APE/Ref-1 protein and the failure of DNA repairing might have contributed to apoptosis after cerebral hypoxia and ischemia.