Transforming growth factor (TGF)-β-inducible gene-h3 (βig-h3) product is a secreted protein that is induced by TGF-β in several cell types and implicated in various tissue pathologies. The aims of this study were to determine the effect of TGF-β1 on βig-h3 expression in cultured astrocytes and to examine whether βig-h3 is expressed in the brain after traumatic injury. The results showed that βig-h3 mRNA and protein increased in response to TGF-β1 in U87 human astrocytoma cells and mouse cortical astrocytes. Treatment with other cytokines, including tumor necrosis factor-α and fibroblast growth factor-2, did not enhance the expression of βig-h3 in astrocytes. βig-h3 was significantly expressed in reactive astrocytes at the site of a stab wound in the cerebral cortex of adult rats. These results provide an insight into understanding a novel role for βig-h3 protein in the response of astrocytes to brain injury.