Abstract Epithelia are physiologically exposed to osmotic stress resulting in alteration of cell volume in several aspects of their functioning; therefore, the activation of ‘emergency’ systems of rapid cell volume regulation is fundamental in their physiology. In this review, the physiological response to osmotic stress, particularly hypertonic stress, was described in a salt-transporting epithelium, the intestine of the euryhaline teleost European eel. This epithelium is physiologically exposed to changes in extracellular osmolarity and represents a good physiological model for functional studies on cellular volume regulation, permitting the study of volume regulated ion transport mechanisms in a native tissue. An absorptive form of the cotransporter, homologue of the renal NKCC2, localized on the apical membrane, was found in the intestine of the euryhaline teleost European eel. This cotransporter accounts for the luminal uptake of Cl−; it operates in series with a basolateral Cl− conductance and presumably a basolateral electroneutral KCl cotransport and in parallel with a luminal K+ conductance. The ion transport model described for eel intestine, based on the operation of an absorptive luminal Na+–K+–2Cl−, is basically the same as the model that has been proposed for the thick ascending limb (cTAL) of the mammalian renal cortex. This paper focuses on the role of Na+–K+–2Cl− cotransport in the responses to hypertonic stress in the eel intestine and the role of cytoskeleton (either actin-based or tubulin based) is discussed.