Melatonin has beneficial effects against early brain injury (EBI) by modulating cerebral oxidative stress after experimental subarachnoid hemorrhage (SAH); however, few investigations relate to the precise underlying molecular mechanisms.To date,the relation betweenmelatonin and nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway has not been studied in SAH models.This study was undertaken to evaluate the influence of melatonin on Nrf2-ARE pathway in rats after SAH.Adult male SD rats were divided into four groups:(1) Control group (n =18) ; (2) SAH group (n =18) ; (3) SAH +vehicle group (n =18) ; and (4) SAH + melatonin group (n =18).The rat SAH model was induced by injection of 0.3 ml fresh arterial,non-heparinized blood into the prechiasmatic cistern in 20 sec.In SAH + melatonin group,melatonin was administered i.p.at 150 mg/kg at 2 h and 24 h after the induction of SAH.Brain samples were extracted at 48 h after SAH. Treatment with melatonin markedly increased expressions of Nrf2-ARE pathway related agents,such as Nrf2,heme oxygenase-1 (HO-1),NAD(P)H:quinone oxidoreductase 1 (NQO1),and glutathione S-transferase α-1 (GST-α1).Administration of melatonin following SAH significantly ameliorated EBI,including brain edema,blood-brain barrier (BBB) impairment,cortical apoptosis,and neurological deficits.In conclusion,post-SAH melatonin administration may attenuate EBI in this SAH model,possibly through activating Nrf2-ARE pathway and modulating cerebral oxidative stress by inducing antioxidant and detoxifying enzymes.