Transcellular Cl − secretion is mediated by two steps; 1) the entry step of Cl − into the cytosolic space from the basolateral space across the basolateral membrane by Cl − transporters, such as Na + ‐K + ‐2Cl − cotransporter, and 2) the releasing step of Cl − from the cytosolic space into the luminal (air) space across the apical membrane via Cl − channels. Various experimental techniques have characterized transcellular Cl − secretion: e.g., short‐circuit current techniques and patch clamp techniques provide us useful information on transepithelial ion movements. Many investigators have tried to clarify roles of Cl − channels and transporters located at the apical and basolateral membranes in transcellular Cl − secretion. However, we have little information how Cl − channels/transporters contribute to transcellular Cl − secretion and are regulated by various stimuli such as Ca 2+ and cAMP. In the present study, we tried to simulate transcellular Cl − secretion using mathematical models combined with electrophysiological measurements, providing information on contribution of Cl − channels/transporters to transcellular Cl − secretion, activity of electro‐neutral ion transporters and how Cl − channels/transporters are regulated.