Exposure of rats to an elevated dietary salt intake raised renal cortical g91phox mRNA that was associated with an increased NADPH oxidase activity but decreased SOD mRNA. However, whether there were comparable responses in the renal medulla was not investigated. The aim of this study was to further explore the impact of a raised sodium intake on NADPH oxidase mediated regulation of blood perfusion through not only the renal cortex but also in the medulla where the situation is unclear. This was done by blocking superoxide dismutase activity in Wistar rats fed normal salt diet and in one fed high salt diet where NADPH oxidase had been inhibited. Two groups of male Wistar rats (225-353g) were used with one group (n=9) maintained on a normal salt (0.3% Na) and other group (n=10) fed a high salt diet (3% Na) for 14 days and either group maintained on Apocynin (454gm / l) in drinking water for 7-10 days. Anesthesia was induced with 1ml ip chloralose/urethane (16.5/250mg/ml). The right femoral vein was cannulated for infusion of saline (154mM NaCl) at 3ml/h and supplemental doses of anesthetic. The right femoral artery was cannulated for measurement of blood pressure (BP) and Heart rate (HR). Through a flank incision, the left kidney was mobilized and supported in a cup holder to eliminate respiratory movement and a small cannula was inserted 4.5mm into the kidney for intramedullary (i-m) infusion of saline or drugs at 0.6-1.0 ml/h. Two Laser-Doppler microprobes (each 0.5 mm diameter) were inserted 1.5 and 4.0 mm into the kidney to measure cortical and medullary blood perfusion, respectively. After 90min, baseline measurements were taken, and then diethyl-dithio-carbamate (DETC) a SOD inhibitor was infused i-m, at 1ml/hr for 30 min at increasing doses of 1, 2 and 4 mg/kg/min. Data, means ± SE, were analyzed using a one-way ANOVA test with significance taken at P<0.05. The HSR group treated with Apocynin had significantly (P<0.05) lower baseline level of MBP and CBP than the NR treated with Apocynin. Neither MAP nor HR was significantly affected by the DETC infusions in either group. The CBP in HSR on Apocynin was reduced significantly only after the 4mg/kg/min dose of DETC, by 28±3%, while the CBP in NR on Apocynin did not change in response to any dose of DETC. The MBP in HSR given Apocynin reduced by 20±5% after the 1mg/kg/min dose, by 25±3% after 2mg/kg/min dose and by 36±4% after the 4mg/kg/min of DETC interstitial infusion, while the MBP in NR given Apocynin reduced by 20±3%PU only after the 4mg/kg/min dose of DETC given interstitially. The findings showed the significant role of high salt diet in inducing the oxidative stress that can be demonstrated by the reduction of the medullary and cortical perfusion of HSR in which NADPH oxidase was inhibited compared to that of NR.