Craniofacial growth is influenced by the interaction of muscle and bone tissues. The medial pterygoid (MP) is one of the muscles of mastication attached to the mandible. The purpose of the study was to investigate the relation between the MP and mandible during embryogenesis. Specimens were prepared from fifty fetal mice at embryonic day (ED) 12.5, 13.5, 14.5 and 15.5. Slides were stained with hematoxylin and eosin (H&E) and observed under the light microscope. Immunohistochemistry using desmin, a muscle specific marker, as well as vimentin, a mesenchymal specific marker, were also carried out. Desmin and vimentin mRNA expressions were analyzed by quantitative polymerase chain reaction. Results showed that at ED 12.5, the MP and lateral pterygoid (LP) and tensor veli palatine (TVP) were adjacent to one another. Over time, the LP moved more externally while the TVP moved more medially. At ED 13.5, the mandible started to form while the MP moved towards the developing mandible. At ED 14.5, the palatine shelves were also seen in a horizontal position. Over time, desmin localization was observed at myotendinous junctions in between the MP and Meckel's cartilage (MC) as well as in between the MP and mandible and finally in the center of the muscle. The increase in the expression was supported by desmin mRNA expression. Vimentin was widely distributed in mesenchymal cells with no significant difference among the stages. The results suggest that although the muscles of mastication were still immature, the premature contraction of the MP and the positional relationship provide a dynamic change between the development growth of the mandible and the start of the fusion of the secondary palate.