Although hypoxia-inducible factor-1 alpha (HIF-1 alpha) has been extensively studied in brain injury following hypoxia-ischemia, the role of HIF-1 alpha in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. The present study was under taken to investigate a potential role of HIF-1 alpha in EBI after SAH. Rats (n = 60) were randomly divided into sham+vehicle, SAH+2-methoxyestradiol (2ME2), and SAH+vehicle groups. The SAH model was induced by endovascular perforation and all the rats were subsequently sacrificed at 24 h after SAH. We found that treatment with 2ME2 suppressed the expression of HIF-1 alpha, BNIP3 and VEGF and reduced cell apoptosis, blood-brain barrier (BBB) permeability, brain edema, and neurologic scores. Double fluorescence labeling revealed that HIF-1 alpha was expressed predominantly in the nuclei of neurons and TUNEL-positive cells. Our work demonstrated that HIF-1 alpha may play a role in EBI after SAH, causing cell apoptosis, BBB disruption, and brain edema by up-regulating its downstream targets, BNIP3 and VEGF. These effects were blocked by the HIF-1 alpha inhibitor, 2ME2. (C) 2013 Elsevier Inc. All rights reserved.