Osmolarity changes created by sucrose during the perfusion of isolated rat submandibular glands (SMG) in vitro alter secretion rates much more than predicted by the osmotic theory of fluid production. However, these are in accord with a theory involving AQP5 feedback control of paracellular fluid transfer (Hill & Shachar-Hill 2002). The changes in transport rate can be predicted with parameters determined earlier for this gland (Murakami et al. 2001) and a model of the SMG system is presented. Experiments were performed with SMG from genetically selected rats that have very low levels of AQP5 as determined by Western blotting (Murdiastuti, K. et al. 2002). The fluid secretion rates after osmolarity changes were those expected for the osmotic theory. We suggest that control of paracellular flow has been lost in these low AQP5 rats which have reverted to osmotic fluid production. Retrograde injection of Hg ions into the duct partially inhibited AQP5, leading to a concentration-dependent reduction in flow rates. However, reduction of fluid secretion after osmolarity changes was still close to that of normal rats. The results suggest the involvement of a feedback loop including AQP5 and paracellular fluid transport. [J Physiol Sci. 2006;56 Suppl:S70]