Heme oxygenase-1 (HO-1) induction can attenuate the development of angiotensin II (Ang II)-dependent hypertension. However, the mechanism by which HO-1 lowers blood pressure is not clear. The goal of this study was to test the hypothesis that induction of HO-1 in the kidney can attenuate the increase in reactive oxygen species (ROS) generation that occurs during Ang II-dependent hypertension. Mice were divided into 4 groups, control (Con), cobalt protoporphyrin (CoPP), Ang II, and Ang II + CoPP. CoPP treatment (50 mg/kg) was administered in a single SQ injection two days prior to implantation of an osmotic minipump which infused Ang II at a rate of 1 µg/kg/min. At the end of this period, mean arterial blood pressure (MAP) averaged 93 ±5, 90 ± 5, 146 ±8 and 105 ±6 mmHg in Con, CoPP, Ang II and Ang II + CoPP treated mice. In order to determine if HO-1 induction resulted in a decrease in Ang II stimulated ROS generation in the renal medulla, superoxide production was measured. Medullary superoxide production was increased by Ang II infusion and normalized in mice pre-treated with CoPP. The reduction in Ang II mediated superoxide production in the medulla with CoPP was associated with a decrease in extracellular superoxide dismutase protein but an increase in catalase protein and activity. These results suggest that reduction in superoxide and/or hydrogen peroxide production in the renal medulla may be a potential mechanism by which induction of HO-1 with CoPP lowers blood pressure in Ang-II dependent hypertension.