Hearing loss related to aging is the most common sensory disorder among elderly individuals. Macrophage migration inhibitory factor (MIF) is a multi-functional molecule. The aim of this study was to identify the role of MIF in the inner ear. MIF-deficient mice (MIF-/- mice) of BALB/c background and wild-type BALB/c mice were used in this study. Expression of MIF protein in the inner ear was examined by immunohistochemistry in wild-type mice (WT). The hearing function was assessed by the click-evoked auditory brain-stem response in both MIF-/- mice and WT at 1, 3, 6, 9, 12, and 18 months of age. Morphological examination of the cochlea was also performed using scanning electron microscopy and light microscopy. MIF was observed in the spiral ligament, stria vascularis, Reissner's membrane, spiral ganglion cells (SGCs), saccular macula, and membranous labyrinth. The MIF-/- mice had a significant hearing loss as compared with the WT at 9, 12, and 18 months of age. In the MIF-/- mice, scanning electron microscopy showed that the outer cochlear hair cells were affected, but that the inner cochlear hair cells were relatively well preserved. The number of SGCs was lower in the MIF-/- mice. MIF was strongly expressed in the mouse inner ear. Older MIF-/- mice showed accelerated age-related hearing loss and morphological inner ear abnormalities. These findings suggest that MIF plays an important role in the inner ear of mice. (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.