Leptin decreases visceral fat (VF) and increases peripheral and hepatic insulin action. Here, we generated similar decreases in VF using leptin (Lep), β₃-adrenoreceptor agonism (β3), or food restriction (FR) and asked whether insulin action would be equally improved. For 8 days before the in vivo study, Sprague-Dawley rats (n = 24) were either fed ad libitum [control (Con)], treated with Lep or β3 (CL-316,243) by implanted osmotic mini-pumps, or treated with FR. Total VF was similarly decreased in the latter three groups (Lep, 3.11 ± 0.96 g; β3, 2.87 ± 0.48 g; and FR, 3.54 ± 0.77 g compared with 6.91 ± 1.41 g in Con; P < 0.001) independent of total fat mass (by³H₂O) and food intake. Insulin (3 mU ⋅ kg⁻¹ ⋅ min⁻¹) clamp studies were performed to assess hepatic and peripheral insulin sensitivity. Decreased VF resulted in similar and marked improvements in insulin action on glucose production (GP) (Lep, 1.19 ± 0.51; β3, 1.46 ± 0.68; FR, 2.27 ±0.71 compared with 6.06 ± 0.70 mg ⋅ kg⁻¹ ⋅ min⁻¹in Con; P < 0.001). By contrast, reduction in VF by β3 and FR failed to reproduce the stimulation of insulin-mediated glucose uptake (∼60%), glycogen synthesis (∼80%), and glycolysis (∼25%) observed with Lep. We conclude that1) a moderate decrease in VF uniformly leads to a marked increase in hepatic insulin action, but2) the effects of leptin on peripheral insulin action are not due to the associated changes in VF or β3 activation.