Recent studies have showed that inflammatory responses occur in inner ear under various damaging conditions including noise-overstimulation. We evaluated the time-dependent expression of proinflammatory cytokines in noise-exposed rat cochlea. Among several detected cytokines, real-time RT-PCR showed that interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were significantly induced 3 hr after noise exposure, and quickly downregulated to the basal level. Tumor necrosis factor-alpha (TNF-α) was also slightly upregulated immediately after noise exposure. Immunohistochemical analysis showed that IL-6 expression was distinctively induced within the lateral side of the spiral ligament. Sequential expression analysis showed that IL-6 immunoreactivity was initially found in the cytoplasm of lateral wall cells, including Type IV and III fibrocytes, and expanded broader throughout the lateral wall, finally to the stria vascularis. Because of the negative Iba-1 staining, IL-6 expression in the early-phase was not due to macrophage or microglia activation. IL-6 was also detected in spiral ganglion neurons at 12 and 24 hr after noise exposure. Our data demonstrates the production of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in early phase of noise overstimulated cochlea. IL-6 expression was observed in the spiral ligament, stria vascularis, and spiral ganglion neurons. These cytokines, produced by the cochlear structure itself in response to noise exposure, may initiate an inflammatory response and have some role in the mechanism of noise-induced cochlear damage. © 2006 Wiley-Liss, Inc.