Increasing afferent renal nerve activity decreases efferent renal nerve activity (ERNA) and increases urinary sodium excretion. Activation of renal pelvic mechanosensory nerves is impaired in streptozotocin (STZ) treated rats, model of type I diabetes. Decreased activation of renal sensory nerves would lead to increased ERNA, sodium retention and hypertension. We examined whether the reduced activation of renal sensory nerves in STZ rats was due to increased renal angiotensin activity and whether activation of the renal sensory nerves was impaired in obese Zucker diabetic fatty (ZDF) rats, model of type II diabetes. In an isolated renal pelvic wall preparation from rats treated with STZ for 2 wks, PGE₂ failed to increase the release of substance P, from 5±1 to 6±1 pg/min. In pelvises from Sham-STZ rats, PGE₂ increased substance P release from 6±1 to 13±2 pg/min. Adding losartan to the incubation bath increased PGE₂-mediated release of substance P in STZ rats, from 5±1 to 10±2 pg/min, but had no effect in Sham-STZ rats. In pelvises from obese ZDF rats (22-46 wks old), PGE₂ increased substance P release from 12.0±1.2 to 18.3±1.2 pg/min which was less than that from lean ZDF rats, 10.3±1.6 to 22.5±2.4 pg/min. Losartan had no effect on the PGE₂-mediated substance P release in obese or lean ZDF rats. Conclusion: The mechanisms involved in the decreased responsiveness of the renal sensory nerves in STZ rats involve activation of the renin angiotensin system in STZ but not in obese ZDF rats.