Objective To elucidate the relationship between f luoride and cell apoptosis of ameloblasts and to further study the mechanism of dental fluorosis. Methods By establishing an experimental m odel of fluoride intoxication in pregnant C57BL/6N, we observed apoptosis in the fetal secretory ameloblasts in mice by means of transmission electron microscop e and TUNEL. Results High fluoride exposure in pregnant mic e could cause subameloblastic cysts in first lower molar of fetal mice. Programm ed cell death (PCD) occurred in the disturbed ameloblasts above cysts. Conclusion Intoxicat ion mechanism of fluoride on ameloblasts may occur by means of PCD.