Objective: To investigate the morphological change on embryonic palatal development in mice of exposure to RA, and to detect the significance of the expression of TGF beta1, TGF beta3, EGF and BCL2 in the embryonic palate in RA-induced cleft palate. Methods: The stages of palatal development were examined by light microscopy. S-P immunohistochemistry and in-situ hybridization were used to detect spatio-temporal patterns of expression of TGF beta1, TGF beta3, EGF and BCL2 in the embryonic palate. Results: The exposure of the fetus to RA resulted in the formation of small palatal shelves which did not make contact or fuse with each other to form an intact palate. RA could regulate the embryonic palatal expression of genes involved in RA-induced cleft palate. Conclusion: RA can inhibit the proliferation of MEPM cells so that they form bi-palatal shelves which do not contact or fuse with each other, resulting in the formation of a cleft palate. RA can regulate the spatio-temporal patterns of expression of TGF beta1, TGF beta3, EGF and BCL2 in embryonic palatal processes and the change of spatial expression of these genes in embryonic palatal processes are involved in RA-induced cleft palate.