Brain edema is a critical condition resulted from blood-brain barrier (BBB) disruption after traumatic brain injury (TBI). Several astrocyte-derived factors are involved in BBB function. We previously confirmed the involvements of endothelin ET_B receptor for BBB disruption. In this study, the effects of BQ788, an ET_B receptor antagonist on brain edema and astrocyte-derived factors were examined. As a model of TBI, fluid percussion injury (FPI) was performed on mouse cerebrum. BBB disruption and brain edema were evaluated by Evans blue extravasation and brain water content, respectively. Expressions of astrocyte-derived factors were confirmed by Real-time PCR and immunohistochemistry. To confirm therapeutic efficiencies, intraventricular (i.c.v., 15 nmol/day) or intravenous (i.v., 5 mg/kg/day) administration of BQ788 were performed from 2 to 5 days after FPI. BQ788 ameliorated FPI-induced BBB disruption and brain edema but not affected blood pressure. ET_B receptors were mainly distributed in astrocytes and BQ788 appropriately controlled expressions of several astrocyte-derived factors after FPI. Thus, blockade of ET_B receptor is expected to be a novel therapeutic strategy for brain edema.