Hypoxia-ischemia remains a major perinatal mortality and chronic disability cause in newborns. Hypothermia is the only clinically therapeutic approach but new therapy must be developed. Our aim was to study the neuroprotective role of lactate in rat neonatal hypoxic-ischemic model and to determine the best pattern to counteract brain damages. Interestingly, lactate was much more neuroprotective when administered after hypoxia (curative) than before (preventive). Single versus 48h injection of lactate were compared. Lactate shows significant and important neuroprotection (ADC, FA, immunohistochemistry, behavioral studies).