OBJECTIVE: The neonatal rat model of hypoxic-ischemic brain damage (HIBD) is a useful tool for studying hypoxic-ischemic encephalopathy of the newborn. Although many reports have studied the pathological and biochemical outcomes on HIBD in the animal model, little research has focused on assessing the long-lasting behavioral changes. This study was designed to examine the long-lasting behavioral alternations following HIBD in neonatal rats. METHODS: Twenty-four 7-day-old SD rats were randomly assigned into a Control group (n = 12) and a HIBD group (n = 12). The rats in the HIBD group were subjected to ligation of the left carotid artery, followed by 2 hrs hypoxia exposure. A battery of behavioral tests, including the T-maze test and sensorimotor tests, were performed at postnatal age 3 - 4 weeks. Histological changes and their correlations with the results of behavioral tests were evaluated. RESULTS: In the behavioral tests, HIBD rats performed significantly worse than control rats. In the T-maze test, the HIBD group differed significantly from the Control group, achieving the correct percentage on the 3rd and 4th days after hypoxia-ischemia (HI) of 68.3%±26.2% vs 86.7%±15.6% ( P =0.049) and 66.7%±15.6% vs 98.3%±5.7% (P < 0.001), respectively. In the sensorimotor tests, asymmetries of foot-faults and limb-placing were detected in HIBD rats. The postural reflex test showed an abnormal motor function in HIBD rats. The neurons number in the DG area of the hippocampus (39.7 ± 5.9) and the cortex ( 12.7±3.3) was significantly reduced in the HIBD group when compared with those in the Control group (50.9 ± 4.1 and 18.2 ± 3.3, respectively). There was no correlation between the behavioral tests results and histological changes. CONCLUSIONS: HI injury in neonatal rats may cause long-lasting deficits of learning, spatial and sensorimotor function. Behavioral testing is an important measure of outcome following HIBD, and behavioral testing measures may be used to test the efficacy of HIBD treatment.