Background: Astragali Radix, the dried root of Astragalus membranaceus Bunge, is a widely used herbal and traditional medicine and is viewed as a primary energizing medicinal herb that invigorates vital energy. Objective: We investigated the effects of Astragali Radix administered on ischemia-induced brain injury in a mouse model. Materials and Methods: Ischemic brain injury was induced by middle cerebral artery occlusion (MCAO) for 2 h. Methanol extracts of Astragali Radix (Amex) were then orally administered daily for 3 days. Relative cerebral blood flow was measured under ischemic conditions. Infarct volumes were measured by triphenyltetrazolium chloride staining. Changes in brain edema, brain water content, and neurological deficit (ND) scores were also measured. Aquaporin-4 (AQP-4) protein and mRNA expression were evaluated and histological changes visualized by staining with hematoxylin and eosin or cresyl violet. Results: Oral administration of Amex for 3 days after MCAO significantly reduced brain infarct volumes, edema indices, and water contents and suppressed the expression of AQP-4 at the protein and mRNA levels. However, MCAO-induced increases in ND scores were not ameliorated by Amex. Conclusion: Oral administration of Amex following onset of brain injury reduced infarct volume and brain edema. Our results suggest that reduction of AQP-4 protein and mRNA expression is a possible mechanism for these effects.