There are endogenous intracellular mechanisms that provide cells with protection from stress, as well as repair from damage. These pathways often involve stress proteins and neurotrophic factors. The present study used Western blot analysis to examine changes in glial cell line-derived neurotrophic factor (GDNF) following noise overstimulation. A noise exposure was utilized which causes a temporary threshold shift and has been previously shown to upregulate heat shock protein 72 in the rat cochlea. This noise exposure also provides protection from a second noise exposure that would otherwise cause a permanent threshold shift. Experimental animals were assessed 2, 4, 8 and 12 h after cessation of noise exposure. Control animals received the same treatment except for the noise exposure and were assessed at the 8 h time point. A moderate expression of GDNF was observed in the normal cochlea. No significant change in GDNF levels was observed at 2 or 4 h following noise overstimulation. However, a significant increase was found at 8 h. At 12 h following noise overstimulation, GDNF levels were no longer significantly elevated from normal. These results suggest that GDNF is involved in the endogenous stress response in the cochlea and are consistent with the protection that exogenously applied GDNF has been shown to provide.