Objective To investigate the effect of alpha-lipoic acid on oxidative stress and cerebral edema after hypoxic-ischemic brain damage (HIBD)in neonatal rats.Methods A total of 108 neonatal 7-day-old Wistar rats were randomly divided into 3 groups:sham-operated group(sham, n=36), HIBD group(HIBD, n=36) and alpha-lipoic acid-treated group (treated group, n=36).Each group was divided into 3 sub-groups (n=12, per sub-group) based on different time points after HIBD (1 d, 3 d, 7 d).HIBD rat models were established by ligating the left common carotid artery, The sham-operated group and the HIBD group were treated with normal sodium injection intraperitoneally; treated group were treated with alpha-lipoic acid 100 mg/kg every 12 hours in 5 days.Animals were sacrificed at different time points.Changes of brain water content were determined by dry-wet weight method.And the levels of SOD,MDA,GSH-PX were measured.Results HIBD group showed an upward trend in brain water content and the level of MDA after HIBD, were higher than that of sham-operated group at each time point (P<0.05).Meanwhile, the levels of SOD and GSH-PX showed the downward trend in HIBD group.The levels of brain water content and the level of MDA in treated group were significantly lower than HIBD group at each time point ( P<0.05 ) .And the levels of SOD and GSH-PX in treated group were significantly higher than HIBD group at 3 d and 7 d.on the contrary , the level of MDA in treated group was significantly lower than HIBD group at 3 d and 7 d.Conclusion Alpha-lipoic acid can amiliorate cerebral edema, so it can prevent HIBD.The neuronal protective mechanism might be reverse oxidative imbalance in the brain of neonatal rats with HIBD.