Sensorineural hearing loss (SNHL) causes irreversible hearing impairment that is in many cases and thus significantly reduces the quality of life. Our previous studies have reported that repeated exposure to moderate noise reduces the number of synapses between inner hair cells (IHC) and the cochlear nerve (IHC synapses). This study aimed to clarify the cause of this decrease in the number of synapses due to repeated noise exposure. IHC synapses were visualized by immunostaining with specific antibodies against c-terminal binding protein 2 (CtBP2) and glutamate receptor subunit A2 (GluA2). Repeated noise exposure increased the expression of the interleukin-1β gene (Il1b) and cyclooxygenase (COX)-2 protein in the IHC, thereby causing intracochlear inflammation. Treatment using continuous PLX3397 (290 ppm in MediDrop sucralose, a colony-stimulating factor-1 receptor inhibitor) for 1 week decreased the number of macrophages in the cochlea and, significantly, the number of IHC synapses due to repeated noise exposure. NS-398 (5 mg/kg, COX-2 inhibitor) significantly suppressed the loss of IHC synapses caused by repeated noise exposure. In addition, intraperitoneal administration of lipopolysaccharide (1 mg/kg) increased cochlear Il1b at 4 h post-dose and significantly decreased the number of IHC synapses at 24 h post-dose. These data suggest that intracochlear inflammation is involved in the reduction of the number of IHC synapses.