This study was designed to disclose the specific changes of distortion product otoacoustic emission (DPOAE), including DP-gram and I/O-gram in guinea pigs treated with GM for 10 and 17 days. Forty guinea pigs were divided into four groups:group I (treated with GM for 10 days), group II (treated with normal saline for 10 days), group III (treated with GM for 17 days), group IV (treated with normal saline for 17 days). DPOAE including DP-gram and DP-I/O was recorded by use of CELESTA 503 Cochlear Emission Analysis and the out hair cell loss was numerated. (1) The amplitude in group I showed significant reduction at frequencies of 4, 6, 8 kHz. There were significant differences, compared to group II (t=2.52, 1.92, 2.10, P<0.05). The amplitude in group III also decreased at frequencies of 3, 4, 6, 8 kHz. There were also significant differences compared to group IV (t=3.27, 2.81, 2.92, 3.13, P<0.01). The amplitude of DP-I/O in group I and group III at different frequencies and stimulus levels showed reduction. (2) At the level L1 <60 dB SPL, the stimulus levels to elicit a 0 dB response in group I and group III were higher than those in corresponding control groups, respectively. (3) The mean of threshold shift was 5.0+/-3.8 dB in group I and 25.0+/-6 dB in group III at 8 kHz frequency. (4) The out hair cell loss was 22.16% in group I and 48.36% in group III, both showed significant difference as compared to controls, respectively (P<0.01). The employment of DPOAE can be a useful tool in monitoring ototoxicity of GM for its sensitivity and specificity in guinea pigs treated with GM. The changes in DPOAE were consistent with those in histology.