Abstract: Objective: To set up the retinoic acid (RA)-induced exencephaly model in KM mice,and analyze the toxicity of RA to fetus and its mother. Methods: The KM mice were randomly divided into test and control groups. The mice were orally treated with a single dose of 20,30,40 and 50 mg/kg of all-trans-RA which dissolved in peanut oil at a selective time of gestational day (GD)7.50 d,GD7.75 d,GD8.00 d or GD8.50 d. The mice in control group were administrated with a volume of peanut oil,equal to the dose of RA. Results: RA could lead to exposed exencephaly at different development stage and different drug dosage,and the incidence of exencephaly was increased with the increasing of RA dosage and decreased with the addtion of the gestational age. The ideal animal model of exencephaly was established by administrating 30 mg/kg RA to GD 7.75 d mice. In addition,the fetus in test group was displayed an open neural tube and the GD16.50 d fetus was showed a exposed brain tissue at cephalosume. The fetal cranial bone and skin were incomplete developed. Conclusions: The mouse model of exencephaly was sucessfully established and laid the basis for the further study.