The present study demonstrates that the protein expression of HO-1 and Nrf2 was positively modulated by RESV treatment in neonatal rats subjected to HI, which may have contributed to its neuroprotective activity, with corresponding decreases in infarct volume and cerebral oedema, elevated levels of antioxidants, suppression of inflammatory markers and improved neuronal morphology. This evidence concerns the gene NFE2L2 and brain edema.