Objective To explore the effect of Quercetin on the long-term memory and PARP-1/AIF signal path in neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods Fifty-six 7-day-old SD rats were randomly divided into sham-operation group, HIBD group, low dose of Quercetin group (20 mg/kg), and high dose of Quercetin group (40 mg/kg), each of 14 rats. Except for sham-operation group, in the other groups HIBD model were made by right common carotid artery ligation and anoxiate. The Quercetin groups were injected with the corresponding doses of Quercetin immediately once a day continuously for 7 days after the model was made,. Sham-operation group and HIBD group were intraperitoneally injected with normal saline at the same time. Neural function was evaluated by Hanging wire test and Vertical pole test at 21 days old. The capacity of learning and memory was detected by Morris water maze at 28 days old, and then rats were killed and brains were taken. HE was used to observe the pathological changes of hippocampus. Western blot were used to detect the expression of PARP-1 and AIF in hippocampus. Results Compared with sham-operation group, the neural function and learning and memory ability decreased significantly in HIBD group. Those ability in both low dose and high dose of Quercetin groups were remarkably increased in comparison with HIBD group, and there were statistic differences (P??0.05). Conclusion Quercetin could improve long-term learning memory in newborn rats with HIBD, and the mechanism may be down-regulation of PARP-1/AIF cell apoptosis signaling pathway, inhibition of neuronal apoptosis, and thus play a role in protection of brain.