Objective To observe the effect of overdose fluoride on the expression of enamelin in rat mandibular incisor. Methods Twenty Wistar rats were divided randomly into two groups. Animals were maintained in standard environment with free access to food and distilled water(control group) or water added with 100 mg/L F-(experimental group). The rats were killed in the eighth week. HE staining was used to observe the morphology of ameloblasts.Immunohistochemical staining was adopted to study the expressions of enamelin in rat incisor. Results The amelo-blasts of the treated rat were arranged in multi-layer. The ameloblasts in group Ⅱ were thinner than those in groupⅠ. The structure of enamel matrix was in disorder. The expressions of enamelin in ameloblasts and odontoblasts were obviously inhibited in group Ⅱ(P