The development of sensorineural hearing loss is a serious problem because it significantly reduces the quality of life. Age-related, noise-induced, and drug-induced sensorineural hearing loss has been reported to decrease inner hair cell synapses (IHC synapses) in its early stages. This study aimed to determine the cause of this decrease in IHC synapses. We prepared the mice in which repeated exposure (1-h exposure per day, 5 times) to moderate noise (8-kHz octave band noise, 90 dB sound pressure level) induced gradual hearing impairment along with a loss of IHC synapses. Treatment with PLX3397 (macrophage-depletion drug, 290 mg/kg) significantly improved reduced the number of synapses and hearing impairment caused by repeated noise exposure. Treatment with minocycline (macrophage-activation inhibitor, 50 mg/kg) significantly improved reduced the number of synapses and hearing impairment caused by repeated noise exposure. These results suggest that intracochlear macrophages are activated by noise exposure and may negatively regulate the number of IHC synapses.