Angiotensin II AT₂ receptors have been implicated to play a role in the regulation of renal/cardiovascular functions under pathological conditions. The present study is designed to investigate the function of the AT₂ receptors on renal sodium excretion and the AT₂ receptor expression in the cortical membranes of streptozotocin (STZ) induced diabetic rats. The STZ treatment led to a significant weight loss, hyperglycemia, and decrease in plasma insulin levels comparing with control rats. STZ-induced diabetic rats had significantly elevated basal UF, U_NaV, FE_Na, and urinary cGMP comparing with control rats. Infusion of PD123319, an AT₂ receptor antagonist, caused a significant decrease in U_NaV (µmole/min) in STZ-induced diabetic rats (1±0.09 vs. 0.45±0.1) but not in control rats (0.35±10.05 vs. 0.4 ±0.07). The decrease in U_NaV was associated with a significant decrease in urinary cGMP levels (pmole/min) in STZ-induced diabetic rats (21±2 vs. 10±0.8) but not in control rats (11.75±3 vs. 12.6±2). The infusion of PD123319 did not alter GFR (STZ: 0.3±0.02 vs. 0.25±0.03; control: 1.4±0.05 vs. 1.5±0.09 ml/min) or MAP (STZ: 82±3 vs. 79±3.5; control: 90±4 vs. 89±4 mmHg) suggesting a tubular effect of the drug. Western blot analysis using AT₂ receptor antibody revealed a significantly enhanced expression of the AT₂ receptor protein (~45kDa) in brushborder (~50 folds) and basolateral membranes (~80 folds) of STZ-induced diabetic comparing with control rats. In conclusion, our data suggest that the tubular AT₂ receptors in diabetic rats are profoundly enhanced and possibly via a cGMP pathway promote sodium excretion in this model of diabetes.