The effects of endothelin (ET)-3 and an ETB receptor agonist on astrocytic activation in rat caudate putamen were examined by an immunohistochemical staining of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes. A single injection of 40 pmol ET-3 into rat caudate putamen increased the number of GFAP positive cells compared to that in the contralateral saline-injected side. Ala1,3,11,15-ET-1 (40 pmol), an ETB receptor agonist, also increased the number of striatal GFAP positive cells. The increases in GFAP positive cells were maximum (about 150% of the control side) in 1–2 weeks after injections of the ETs, and then reduced in 4 weeks. A continuous infusion of BQ788, an ETB receptor antagonist (23 nmol/day), into the lateral ventricle of the cerebrum antagonized the effect of Ala1,3,11,15-ET-1, while 80788 also reduced the number of GFAP positive cells in saline-injected caudate putamen. Intrastriatal injection of 40 pmol Ala1,3,11,15-ET-1 did not affect the number of cells stained by B4 isolectin from Griffonia simplicifolia, which labels activated microglia/macrophages. Intraperitoneal administration of 5 mg/kg per day chloroquine and 0.2 mg/kg per day colchicine did not affect the action of Ala1,3,11,15-ET-1. These results suggest that activation of ETB receptors is involved in the induction of reactive astrocytes.