The role of glucocorticoid receptors (GR) in the protective effect of restraint stress (RS) before acoustic trauma was studied in spiral ganglion neurons of CBA mice. RS increased corticosterone and protected against elevated auditory brain stem thresholds caused by acoustic trauma. This protection was inhibited by the pre-treatment with a corticosterone synthesis inhibitor (MET) and a GR antagonist (RU486). RS followed by acoustic trauma caused an immediate increase in corticosterone that triggered nuclear translocation of GR, without a change in the expression of GR protein. RU486+MET before RS and acoustic trauma caused an immediate increase in GR mRNA followed by increased GR protein expression (24 h post-trauma). GR signaling was further characterized by analyzing NFkB nuclear translocation and protein expression. NFkB nuclear translocation was reduced after i) acoustic trauma, or ii) pre-treatment with RU486+MET before RS and acoustic trauma. Contrary, RS protected against the trauma induced NFkB reduction of its nuclear translocation in IkB-dependant manner. RU486+MET caused a simultaneous decreased IkB expression and NFkB nuclear translocation demonstrating an interference with the IkB mediated activation of NFkB. In summary, RS protects the cochlea from acoustic trauma by increasing corticosterone and activating GR. These results emphasis how GR activity modulates hearing sensitivity and its importance for the rationale use of glucocorticoids in inner ear diseases.