In normal rats, vasopressin and hyperosmolality enhance urea permeability (Purea) in the terminal, but not in the initial IMCD, a process thought to occur through the UT-A1 urea transporter. In the terminal IMCD, UT-A1 is present as 97 and 117 kDa glycoproteins. However, in the initial IMCD, only the 97 kDa form is detected. During streptozotocin induced diabetes mellitus, UT-A1 protein abundance is increased and the 117 kDa UT-A1 glycoprotein appears in the initial IMCD. We hypothesize, that the 117 kDa glycoprotein mediates the vasopressin- and osmolality-induced changes in Purea. Thus, in the present study, we measured Purea in in vitro perfused initial IMCDs from diabetic rats by imposing a 5 mM bath-to-lumen urea gradient without any osmotic gradient. Basal Purea was similar in control vs. diabetic rats (3±1 vs. 5±1 x10^-5 cm/sec, n=4, p=NS). Vasopressin (10 nM) significantly increased Purea to 16±5 x10^-5 cm/sec, n=4, p<0.05 in diabetic, but not in control rats. Forskolin (10 µM, adenylyl cyclase activator) also significantly increased Purea in diabetic rats. In contrast, increasing osmolality to 690 mOsm/kg H₂O did not change Purea in diabetic rats. We conclude that initial IMCDs from diabetic rats have vasopressin- and forskolin-, but not hyperosmolality-stimulated Purea. The appearance of vasopressin-stimulated Purea in initial IMCDs correlates with an increase in UT-A1 protein abundance and the appearance of the 117 kDa UT-A1 glycoprotein in this region during diabetes. This suggests that the 117 kDa UT-A1 glycoprotein is necessary for vasopressin-stimulated urea transport.