Objective To investigate protection against neomycin induced damage of outer hair cells by minocy-cline and potential mechanisms.Methods C57 mice of both genders(n=45)were randomly divided into control,neo-mycin and neomycin+minocycline groups(n=15 in each group).ABR thresholds were obtained and the rate of outer hair cells survival was compared by immunofluorescence staining among the three groups.Cleaved caspase-3 staining and TUNEL staining were used to compare outer hair cells apoptosis.Results ABR thresholds were significantly lower in the neomycin+minocycline group than in the neomycin only group at all frequencies(P<0.05).No cleaved caspase-3 and TUNEL positive cells were detected in the basement membrane in the control group,while the number of such cells increased significantly in the neomycin group,as compared to the group treated with minocycline.Conclusion Minocy-cline provides significant protection against neomycin induced outer hair cell injury,probably mediated by inhibiting the apoptotic pathway.