[Abstract] Objective To investigate the role and possible mechanisms of the dorsal nuclei of lateral lemnniscus(DNLL) in the etiology of tinnitus. Methods A total of 24 male C57 mice with normal hearing were randomly divided into 4 groups: mice in group A were injected intraperitoneally with 350 mg/kg of sodium salicylate; mice in group B were injected intraperitoneally saline in the same way as mice in group A; mice in group C had their right DNLL injected kainic acid，via a brain stereotaxic; mice in group D were injected saline in the same way as mice in group C. After successful homozygous moulding, the mice were subjected to tests such as ABR,open field, elevated cross, forced swimming and sound avoidance reflex. They were sacrificed 14 days after the moulding. Hypothalamus glutamic acid decarboxylase 67 (GAD67) was detected by Western blot. Results The results were compared before and after treatment: ① The ABR thresholds of pure tone 32 kHz, 16 kHz, 8 kHz and click in mice in group A were significantly higher after treatment (all P values <0.05). For the mice in group C, the ABR thresholds at 32 kHz and 16 kHz were elevated after treatment and the differences were statistically significant (all P values <0.05). Mice in group B and group D showed no significant changes in their thresholds. ② From the behavioral results it was concluded that the mice in group A and group C spent significantly less time in the open field and the elevated cross. However, when they were forced to swim, their immobility time was significantly higher and the differences were statistically significant (all P values <0.05). Mice in group B and group D did not show significant changes and the differences were not statistically significant. The sound-beat reflex results showed that the number of false positives was significantly higher in mice in group A and group C. The difference was statistically significant(P values <0.05). However, there was no significant change in the number of false positives in mice in group B and group D. ③ The results of Western blot showed that the GAD67 in the inferior colliculus of mice in group A was significantly reduced, while the NR2A in the inferior colliculus was significantly increased. The GAD67 in the damaged side of DNLL of mice in group C was significantly reduced, but the NR2A in the undamaged side was not significantly changed. Conclusion The mechanism of tinnitus in mice prompted by DNLL destruction may be through the down-regulation of GAD67 expression in the inferior colliculus and the up-regulation of NR2A expression.