Activin plays important roles in reproductive tissues as a stimulator of follicle-stimulating hormone (FSH) secretion. Activin receptor-interacting protein 2 (ARIP2) has been recently identified in mouse tissues as a regulatory protein of activin signal transduction. However, the localization and function of ARIP2 are not well characterized. In this study, we found that ARIP2 mRNA and protein were widely expressed in mouse tissues by reverse transcription-PCR (RT-PCR) and Western blotting. The immunoreactivities of ARIP2 were mainly localized at myocardial cells of heart, Leydig cells in testis, macrophages and epithelial cells of bronchus in lung, renal tubule and collecting tubule, pancreatic islet, adrenal gland, adenohypophysis and hypothalamus by immunohistochemical staining. Furthermore, ARIP2 overexpression down-regulated signal transduction induced by activin A in pituitary gonadotroph LbetaT2 cells and inhibited FSH secretion from primary cultured anterior pituitary cells induced by activin A. These findings suggest that ARIP2 is widely distributed in various tissues and may be a negative regulator of activin action in pituitary cells.