Recently, we reported that oxidative stress decreases D1 receptor numbers and G-protein activation in renal proximal tubules (RPT), resulting in diminished natriuretic response to dopamine in old rats. We tested the hypothesis that exercise in old rats will decrease oxidative stress and restore natriuretic response to D1 receptor agonist, SKF 38393. Old (23-month) rats were subjected to rest (sedentary) or to treadmill exercise followed by measurement of oxidative stress (malondialdehyde, MDA), inflammation (C-reactive protein, CRP), anti-inflammation (interleukine-10, IL-10), antioxidant enzyme (superoxide dismutase, SOD) and natriuretic response to SKF 38393. We found that MDA levels decreased and total SOD activity and Cu/ZnSOD protein increased in RPT of exercised rats. Exercise increased the nuclear levels of Nrf2 transcription factor (which binds to anti-oxidant response elements) in RPT. The levels of CRP decreased and IL-10 increased in RPT of exercised rats. Further, exercise increased the basal bindings of ³H-SCH 23390 and ³⁵S-GTPS (indices of D1 receptor number and G-protein activation, respectively) together with D1 receptor and Gq proteins in RPT membranes. Moreover, SKF 38393 increased sodium excretion in exercised rats. Also, exercise decreased the levels of proteins in the urine of old rats. These results demonstrate that exercise decreases oxidative stress, inflammation and proteinuria, and increases anti-oxidant defense and D1 receptor function in old rats. Therefore, exercise may prove beneficial in preventing age-associated increases in oxidative stress, inflammation and preserving kidney function, in general, and renal D1 receptor responsiveness, in particular.