Abstract—Hypertension related to insulin resistance results from increased sodium retention. Dopamine, by activating D1Areceptors in renal proximal tubules, increases sodium excretion. Recently, dopamine has been shown to augment its own signaling by recruiting intracellular D1Areceptors to cell surface in proximal tubules. In this study, we hypothesized that coupling of D1Areceptors to G proteins and dopamine-induced recruitment of D1Areceptors to the plasma membrane are impaired in obese Zucker rats, resulting in a diminished natriuretic and diuretic response to D1Areceptor agonist, SKF-38393. We also examined effects of rosiglitazone (3 mg/kg per day, 15 days) in restoring the defects in D1Areceptor signaling and function in these animals. In obese rats, D1Areceptors did not couple to G proteins, as shown by a lack of fenoldopam-sensitive [35S] GTP&ggr;S binding. In addition, we observed, by using radioligand binding and immunoblotting, that dopamine recruited D1Areceptors to cell surface in lean Zucker rats but failed to do so in obese rats. Rosiglitazone treatment resulted in restoration of G-protein coupling of D1Areceptors and their recruitment by dopamine in obese rats similar to that seen in lean rats. Furthermore, SKF-38393 failed to increase natriuresis and diuresis in obese rats compared with lean rats. However, in rosiglitazone-treated obese rats, SKF-38393 elicited a diuretic and natriuretic response similar to that in lean rats. Collectively, these results suggest that insulin resistance may be responsible for impaired renal dopamine D1Areceptor signaling and function as treatment with an insulin-sensitizer, rosiglitazone, normalizes these parameters in obese Zucker rats.