Abstract--Hypertension related to insulin resistance results from increased sodium retention. Dopamine, by activating D_1A receptors in renal proximal tubules, increases sodium excretion. Recently, dopamine has been shown to augment its own signaling by recruiting intracellular D_1A receptors to cell surface in proximal tubules. In this study, we hypothesized that coupling of D_1A receptors to G proteins and dopamine-induced recruitment of D_1A receptors to the plasma membrane are impaired in obese Zucker rats, resulting in a diminished natriuretic and diuretic response to D_1A receptor agonist, SKF-38393. We also examined effects of rosiglitazone (3 mg/kg per day, 15 days) in restoring the defects in D_1A receptor signaling and function in these animals. In obese rats, D_1A receptors did not couple to G proteins, as shown by a lack of fenoldopam-sensitive [³⁵S] GTPS binding. In addition, we observed, by using radioligand binding and immunoblotting, that dopamine recruited D_1A receptors 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 D_1A receptors 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 D_1A receptor signaling and function as treatment with an insulin-sensitizer, rosiglitazone, normalizes these parameters in obese Zucker rats.