This study demonstrated that (1) pretreatment with NADPH oxidase inhibitor apocynin significantly reduced the injury of BBB integrity and disruption of occludin induced by 2 hours of ischemia, (2) pretreatment with apocynin reduced increase of HIF-1α expression induced by 2 hours of ischemia, (3) apocynin could also inhibit the MMP-2 upregulation after 2 h ischemic stroke, and (4) HIF-1α is not colocalized with bigger blood vessels. The gene discussed is MMP2; the disease is ischemic stroke.