Abstract: Objective　To investigate the effects of caffeine citrate (CC) on the neuronal proliferation and apoptosis and longterm learning ability in neonatal rats with hypoxia-ischemic brain damage (HIBD). Methods　Forty-eight 7-day-old Sprague-Dawley neonatal rats were randomly divided into 3 groups: sham operation group (n=16), HIBD group (n=16), HIBD + caffeine citrate group (CC group, n=16). Rats in HIBD and CC groups received ligation of left common carotid artery followed by 2 hours of hypoxia to establish HIBD model. Rats in CC group were injected intraperitoneally with CC (20 mg/kg) before and at 0 min, 24 h, 48 h, and 72 h after hypoxia-ischemic (HI), and rats in the other two groups were injected intraperitoneally with an equal volume of normal saline at the corresponding time. Meanwhile, from postnatal day 10, each rat was injected intraperitoneally with 5-bromo-2’-deoxyuridine (BrdU) (50 mg/kg) for 5 consecutive times, once every 12 h. On postnatal day 12, BrdU in the hippocampal dentate gyrus and cleaved caspase-3 in the hippocampal CA1 area were detected by immunohistochemistry, and neuronal apoptosis in hippocampal CA1 area were detected by TUNEL staining. On postnatal day 28, long-term learning and memory ability of rats was tested by Y maze. Results　There was significant difference in the number of BrdU-positive cells in brain tissues of rats among three groups (F=101.38, P<0.01). The BrdU-positive cells in HIBD group and CC group were significantly more than those in sham operation group (P<0.05). There was significant difference in the number of cleaved caspase-3-positive cells in hippocampal CA1 area among three groups (F=379.77, P<0.01). The cleaved caspase-3-positive cells in CC group were significantly fewer than those in HIBD group but significantly more than those in sham operation group (P<0.05). The TUNEL-positive cells in hippocampal CA1 area were significantly different among three groups (F=505.92, P<0.01) which was most in HIBD group and fewest in sham operation group and significant difference was found through multiple comparison (P<0.05). The total learning number of avoiding electric shock tested by Y maze was significantly different among three groups (F=32.05, P<0.01) which was most in HIBD group. Correct response rate was significantly different among three groups (F=24.99, P<0.01) which was lowest in HIBD group. Conclusions　Caffeine citrate can improve the ability of long-term learning and memory in neonatal rats with hypoxia-ischemic brain damage, the mechanism of which may be related to reducing the neuronal  apoptosis after hypoxia ischemia.