Gamma-aminobutyric acid (GABA) is one of major inhibitory neurotransmitter in the central nervous system and constitutes the cochlear efferent system. Glutamate excitotoxicity is implicated in the pathogenesis of acoustic injury of the cochlea. The present work investigated whether GABA(A) agonist muscimol can alleviate acoustic injury. Mice were exposed to a 4 kHz pure tone of 128 dB SPL for 4h. Muscimol and/or bicuculline, a GABA(A) antagonist, were intraperitoneally administered immediately before the onset of acoustic overexposure. The threshold shifts of the auditory brainstem response (ABR) and cochlear morphology after acoustic overexposure were then evaluated. Muscimol significantly decreased the ABR threshold shift and inhibited swelling of the afferent dendrites induced by acoustic overexposure. In addition, bicuculline inhibited the effects of muscimol. These findings suggest that activation of GABA(A) receptors reduces acoustic injury of the cochlea.