The aim of the study was to examine the effects of weight reduction by exercise and diet on metabolic control in obese subjects with insulin resistance, particularly investigating if changes in serum leptin concentrations were directly associated with improvements in metabolic control. Twenty obese men (48 ± 8 yr; body mass index 32.1 ± 3.9 kg/m²) with previously diagnosed type II diabetes mellitus were assigned to a 4-wk intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/day; 50% carbohydrates, 25% protein, 25% fat; polyunsaturated-to-saturated fatty acid ratio 1.0). Intervention induced significant reductions in body weight and serum leptin levels, and improvements in lipoprotein profile and glucose control. Reductions in leptin levels were directly associated with reductions in serum triglycerides and cholesterol, a finding that was independent of improvements in glucose control. These data show that serum leptin concentrations can be reduced with caloric restriction and exercise in male patients with type II diabetes, and they suggest a direct relationship between leptin and lipoprotein metabolism that is not solely due to weight reduction.