Abstract: Objective To observe the effect of overdose fluoride on the expression of amelogenin in rat mandibular incisor and to explore the probable mechanism of dental fluorosis. Methods Six Wistar rats were divided randomly into two groups. Animals were maintained in standard environmental conditions with free access to food and water（control group） or water added with 100 mg/L F（- experimental group）. The rats were killed at the end of eighth week. Using realtime polymerase chain reaction（PCR） to observe the effect of overdose fluoride on the expression of amelogenin in rat mandibular incisor. Results The expressions of amelogenin in rat mandibular incisor were obviously inhibited in experimental group（P<0.05）. Conclusion The overdose fluoride inhibits the secretion of amelogenin and leads to the abnormal development of enamel matrix.