Accumulating studies demonstrated that PAR complex contributed to the establishment and maintenance of cell polarity which was fundamental to many aspects of cell and developmental biology. The purpose of this study was to investigate whether dexamethasone (DEX) could downregulate the PAR complex and disrupt cell polarity in palatal epithelium during palatal fusion in mice. The C57BL/6J mice were selected for the experiment. Pregnant mice in control group and DEX-treated group were injected intraperitoneally with 0.9% sodium chloride 0.1 mL, which contained DEX 6 mg/kg respectively, every day from E10 to E12. The palatal epithelia morphology was observed with hematoxylin and eosin and scanning electron microscopy. Immunofluorescence staining, western blot, and real-time polymerase chain reaction were performed to detect the expression of PAR3/PAR6/aPKC. After being treated with DEX, the palatal shelves showed delayed development and became shorter and smaller. During the process of palatogenesis, PAR3 and PAR6 expressed in the palatal epithelium, and aPKC expressed in both the epithelium and the mesenchyme. Dexamethasone could downregulate the expression levels of PAR3/PAR6/aPKC in both protein and gene level. In conclusions, DEX affected the PAR complex of mouse embryonic palate, and could perturb the PAR complex and the cell polarity of medial edge epithelium cells, and caused the failure of palatal fusion.