Salicylate is a well-known substance to produce reversible tinnitus in humans and animals. It has been shown that systemic application of salicylate changes the neuronal spontaneous activity in several parts of the auditory pathway. Salicylate has also a direct influence on cochlear outer hair cell electromotility. The effects observed in the central auditory structures in vivo could therefore be based upon the change in afferent cochlear input to the auditory system and in addition by a direct action of salicylate on neurons within the auditory pathway. The present study investigated the direct effect of salicylate application on the spontaneous activity of mouse inferior colliculus neurons in brain slices. Out of 92 neurons, 87% responded statistically significantly to the superfusate by changing their firing rates. 70% increased and 17% decreased their firing rates, respectively. Salicylate superfusion induced a general increase of electrophysiological activity within the inferior colliculus brain slice preparation which was similar to those obtained during systemic application of salicylate. The results suggest that the salicylate sensitivity of inferior colliculus neurons can modulate to a great extent the salicylate-induced generation of tinnitus.