Dept. of Oral Medicine,Hospital of Stomatology, Tongji University, Shanghai 200072, China)[Abstract] Objective To investigate the effects of overdosed fluoride on the expression of MMP-20 and TIMP-2 in rat incisor. Methods 20 Wistar rats were randomly divided into experiment group and control group. The distilled water was given in control group. 100 mg/L fluoride- was given in experiment group. After 8 weeks treatment, the rats were killed. Immunohistochemical staining was used to observe the expression of MMP-20 and TIMP-2 in rat incisors. Results Immunohistochemical results demonstrated the presence of MMP-20 and TIMP-2 protein in ameloblasts, odontoblasts, stratum intermedium and the stellate reticulum of rat incisor. The imagination analysis results showed that the expression of MMP-20 was reduesed in experiment group(P0.05). Conclusion The overdosed fluoride inhibits the secretion of MMP-20 and leads to the disturbed balance between MMP-20, TIMP-2 in rat incisor, which leads to the delay of the amelogenin removal and the enamel demineralization.