Objective: To investigate the protective effects of erythropoietin on nerve apoptosis in hippocampus and the ability of learning and memory impaired by hypoxia-ischemia brain damage (HIBD). Methods: Seven days old Sprague-Dawley rats were divided into hypoxia-ischemia (HI) group (n=11), recombinant human erythropoietin (rh-EPO) treated group (n11), and sham-oper ated control group (n=10). The apoptotic characteristics were observed in the three groups by electron microscope 24 h after hypoxia. The number of rats with spontaneous left-turn, nip-tail left-turn, nip-tail squeal in HI group and rh-EPO treated group was counted respectively 0, 6, 12 and 24 h after hypoxia-ischemia, respectively. Step down test was used to determine escape latency (EL), step down latency (SDL) and both error times of learning and memory in three groups at 75-day old. Results: Two rats in HI group and one in rh-EPO treated group died from continuous convulsion during hypoxia. Iii HI group, a large number of apoptosis nerve cells were observed, which was reduced in rh-EPO treated group. All rats in the two groups had spontaneous left-turn, nip-tail left-turn, nip-tail squeal at the time of hypoxia (rh-EPO treated group vs HI group, 10/10 vs 9/9). Compared with HI group, the rate of spontaneous left-turn was dramatically lower in rh-EPO treated group (rh-EPO treated group vs HI group, 1/10 vs 6/9, P 0.0198). Compared with control group, EL of HI group was longer (P<0.01), SDL was shorter (P<0.01), both error times of learning and memory were more. These abnormalities are corrected in rh-EPO treated group (P<0.01), and were not different with those in control group (P>0.05). Conclusion: rh-EPO can inhibit nerve cell apoptosis induced by HI, alleviate brain scathe, and improve the ability of learning and memory. Rh-EPO might become a new drug to treat hypoxic-ischemic encephalopathy in newborns.