Tissue engineering is a rapidly evolving field involved in the restoration of functions and esthetics of tissues after surgery. Utilizing the oral mucosa as a source of tissue-engineered epithelial cell sheets is beneficial due to the fast healing rate and regenerative capability of the tissue. This study investigated the effect of mesenchymal fibroblasts on epithelial cells taken from rabbit oral mucosa. Rabbit oral epithelial cells were cultured on collagen gels both with oral mucosa fibroblasts (OMFs+) and without (OMFs-). Samples were stained with hematoxylin and eosin and observed under a light microscope. The expressions of cytoskeletal, adhesion, basement membrane and junctional complex as well as cell proliferation protein markers were also determined through immunohistochemistry. Results showed that the OS+ group had epithelial cell sheets that were better developed than those of the OMFs- group. Moreover, cytoskeletal, adhesion, basement membrane, junctional complex and cell proliferation markers were more intensely expressed by epithelial cells in the OMFs+ group than in the OMFs- group, and the expression increased over time. Immunohistochemistry demonstrated how stem cells taken from the oral mucosa contributed to the expression of various cytokines indispensable for the growth of the cells. The epithelial-mesenchymal interaction between the keratinocytes and fibroblasts accounts for the architecture of the epithelial cell sheets.