It is widely accepted that the salivary glands secrete primary saliva by osmosis at the acini, and that some of the salivary fluid flows through the tight junctions (paracellular secretory pathway). The aim of this study was to examine the changes in permeability of the acinar tight junction in rat submandibular glands in vivo by electrical stimulation of parasympathetic and sympathetic secretory nerves. The permeability changes of the tight junctions after the stimulation were also examined. The permeability of the tight junction from the interstitium to the lumen was examined by close-arterial infusion with a small ultrastructural tracer, microperoxidase (MW=1, 630 Da), and this tracer was observed by electron microscopy. In the resting gland, the tracer was observed in the interstitial and intercellular spaces, but not within the lumen (closed tight junction). Intraductal injection of hypertonic sucrose (570-998mOsm) caused a subsequent elevation of the luminal pressure, indicating that osmotic fluid had passed into the lumen. However, the tight junction in the gland remained in the closed state. In the chorda stimulated gland and the stimulated gland of the superior cervical ganglion (stimulated for 2min), the tracer entered the lumen through all the tight junctions, that is, they became permeable to the tracer (the tight junction switched to an opened state). However, the opened tight junction reverted to the closed state after 15-30min. These findings suggest that submandibular acinar tight junctions switch rapidly to an opened state by nerve stimulation and close again within 15-30min after the stimulation, and that the paracellular secretory pathway may be involved in the salivary fluid secretion from the acini.