Objective: To establish a model of immune-mediated inner ear disease(IMIED) and to study the change of interferon-γ(IFN-γ) expression in the inner ear.Methods: Twenty guinea pigs were divided into experimental group and control group with paired design.The round windows of systemically pre-sensitized guinea pigs were locally immunized with keyhole limpet hemocyanin(KLH) in experimental group and PBS in the control group.Then the anti-KLH level and auditory function were determined before immunization and at 2 weeks after immunization.Tissue paraffin sections of temporal bone was made and observed by microscopy,and IFN-γ expression in the inner ears of all guinea pigs was detected by immunohistochemical test after immunization.Results: There were significant differences in the mean value of the threshold of ABRⅢ wave before and after immunization of the experimental group(P<0.05).Judging from mean value plus 2 times of the standard deviation(41.10 dB) of all the guinea pigs for the experiment before immunization,7 animals(12 ears) testified hearing loss and the anti-KLH level of their blood increased significantly compared with before immunization(P<0.05).There were no significant differences in the mean of the threshold of ABRⅢwave and the serum specific anti-KLH level before and after immunization in the same guinea pigs from the control group(P>0.05).The mean of the threshold of ABRⅢ wave and the serum specific anti-KLH level were higher in the experimental group than the data in the control group with the significant differences(P>0.05).There was inflammatory cell infiltration in the inner ears of the guinea pigs after immunized among the experimental group through the observation of the inner ear paraffin section lens and the labyrinthine hydrops in the inner ears of the part of the guinea pigs.Immunohistochemical tests showed that almost no immunoreactivity for IFN-γ was detected in the inner ears of the control group, and the IFN-γ immunoreactivity was detected in the inner ears of the experimental group in such sections as organ of Corti,spiral ligament,stria vascularis,spiral ganglion and around the modiolus small vessel.Conclusion: Local immunotherapy for the round window niche of the guinea pigs which had been sensitized could reach the relatively high success rate for creating the model of immune-mediated inner ear disease.The normal guinea pigs almost have no IFN-γ expression in their inner ears,however,the IFN-γ emerges the incredible expression in the inner ears of the guinea pigs with the immune-mediated inner ear disease.Based on its mechanism,the immune-mediated inner ear disease can be possibly connected with the expression of the IFN-γ.