A phenotypic alteration of astrocytes, “astrocytic activation”, is a common phenomenon observed on brain pathologies. Activated astrocytes reveal important roles in tissue repair processes of damaged nervous system. Modulation of the astrocytic functions by synthetic drugs is expected to affect improvement of brain functions and thus, astrocytic receptors have caught much attention as a new target of neurotrophic drugs. Astrocytes express both endothelin (ET) and its receptors. Recent studies on experimental brain injury models showed that astrocytic ET receptors, especially ET_B receptors, are involved in the activation of astrocytes on brain pathologies. In cultured astrocytes, ETs reproduce the functional alterations characterizing activated astrocytes on brain pathologies; increases in proliferation, morphological changes and stimulation of several gene transcription. These studies suggest that astrocytic ET_B receptors can be one of targets for the drugs ameliorating neuronal damages on brain insults through modulating astrocytic function.