OBJECTIVE: To develop an improved neonatal piglet model of hypoxic ischemic brain damage (HIBD). METHODS: Fourteen 7-day-old piglets were subjected to temporary occlusion of both carotid arteries, followed by mechanical ventilation with low concentration of oxygen ( FiO2 = 0.06) for 30 minutes. Before and after the interventions, the heart rate, temperature, invasive blood pressure, blood gas, and concentrations of blood glucose and lactose were measured, electroencephalogram (EEG) was monitored, and neural behavior scores and pathologic changes of brain tissues were evaluated. RRESULTS: Compared with the pre-intervention status, blood glucose and lactose concentrations significantly increased and the heart rate, mean arterial pressure, PaO2 and basic excess significantly decreased after the hypoxic-ischemic intervention. In addition, the frequency and voltage of EEG decreased 30 min after the intervention. The neural behavior scores were significantly lower at 24 h and 72 h after the intervention. The pathologic scores of the cortex, hippocampus and basal were 2.4 ± 0.6 and 2.0±0.4, 2.0± 0.7, respectively. CONCLUSIONS: We have developed a reliable and reproducible piglet model of HIBD.