The physiological expression of cell division cycle 42 (cdc42) in major salivary glands, and paracellular transport of fluorescein isothiocyanate-dextran (FITC-dextran) in SMIE cells, which regulate cdc42 expression, was investigated to clarify the involvement of cdc42 in salivary production.The physiological expression of cdc42 in the rat submandibular gland, parotid gland, sublingual gland, and SMIE cells was detected using SDS-PAGE and western blotting. The paracellular transport of FITC-dextran in transwells was compared in transfected SMIE cells, exhibiting up- or downregulated cdc42 expression.Cdc42 was expressed in all major salivary glands and SMIE cells. SMIE cells transfected with the cdc42 plasmid had an increase efflux. In addition, SMIE cells transfected with the cdc42 siRNA showed decreased efflux.We suggest that cdc42 enhances paracellular transport in salivary glands without any morphological changes, including cell-cell adhesion.