ObjectiveThis study aimed to prepare a hypoxic brain damage model in the neonatal rat using a new approach, 0% oxygen exposure, and to explore the reliability and advantages of the new model.MethodsSevendayold Wistar rats were randomly exposed to either 7 minutes of 0% oxygen, to the conventional RiceVannucci method (ischemia + 2 hrs hypoxia exposure), or to left common carotid artery ligation (ischemia). Rat pups which were not subjected to any hypoxiaischemia treatment were used as the control group. Brain water content and neuronal apoptosis were measured. Neurofunctional assessment was performed. Brain pathological changes were observed using hematoxylin and eosin staining.ResultsThe water content (88.96±0.29%) and apoptosis of neurons (31.52±5.45%) of the left brain in the 0% oxygen group were significantly higher than those of the ischemic and the control groups (P<0.01), and similar to those in the RiceVannucci group. The water content（88.68±0.24%） and apoptosis of neurons（30.85±5.38%）of the right brain in the 0% oxygen group were significantly higher than those of the RiceVannucci, the ischemic and the control groups（P<0.01）. Both side brains of the 0% oxygen group showed pathological injuries, but only left brain of the RiceVannucci group had pathological changes. No pathological abnormalities were seen in the ischemic and the control groups. Significant neurofunctional impairments were found in the 0% oxygen and the RiceVannucci groups.ConclusionsA hypoxic brain damage model of neonatal rat was successfully prepared using 7 minutes 0% oxygen exposure. The new approach appears to be simple and reliable.