Salt sensitive (SS) hypertension is a vascular diathesis characterized by reduced cardiovascular and renal NO bioavailability and local upregulation of Ang II. We have demonstrated that rats infused with Ang II manifest increased cortical COX-2 expression and activity via NADPH oxidase derived reactive oxygen species (ROS). In the current studies we used Dahl salt sensitive (DS) rats to test the hypothesis that hypertensive SS rats have increased cortical COX-2 upregulation, which is mediated by Ang II and ROS. DS rats were placed on either normal salt diet (0.5% NaCl) or high salt diet (4% NaCl) for six weeks and treated with either the AT1R blocker candesartan (CAN, 10 mg/kg/day) or the SOD mimetic Tempol (1 mmol/L). Hypertensive SS rats had a 2 fold increase in the cortical expression of COX-2 as assessed by western blot. These changes in COX-2 expression were accompanied by a 10 fold increase in COX-2 mRNA expression and a 2 fold increase in the urinary excretion of PGE₂. Treatment with either the AT1R blocker CAN or the SOD mimetic Tempol did not reduce blood pressure but resulted in significant reductions in the cortical expression of COX-2 and the urinary excretion of PGE₂. In conclusion, we have demonstrated that local activation of the renin angiotensin system, via increased ROS generation, mediates COX-2 upregulation in hypertensive SS rats. These studies unveil novel mechanistic pathways that may play a role in the pathogenesis of hypertensive renal injury.