Female mosquitoes gorge on vertebrate blood, a rich nutrient source for developing eggs, but gorging meals increase the risk of predation. Mosquitoes are quick to reduce the flight payload with a potent diuresis. Diuretic peptides of the insect kinin family induce a tenfold reduction in the paracellular resistance of Malpighian tubules and increase the paracellular permeation of Cl−, the counterion of the transepithelial secretion of Na+ and K+. As a result, the transepithelial secretion of NaCl and KCl and water increases. Insect kinins signal the opening of the paracellular pathway via G protein–coupled receptors and the elevation of intracellular [Ca2+], which leads to the reorganization of the cytoskeleton associated with the septate junction (SJ). The reorganization may affect the septate junctional proteins that control the barrier and permselectivity properties of the paracellular pathway. The proteins involved in the embryonic formation of the SJ and in epithelial polarization are largely known for ectodermal epithelia, but the proteins that form and mediate the dynamic functions of the SJ in Malpighian tubules remain to be determined.