BACKGROUND: The effect of dietary fat and carbohydrate on glucose metabolism has been debated for decades. OBJECTIVE: The objective was to compare the effect of 3 ad libitum diets, different in type and amount of fat and carbohydrate, on insulin resistance and glucose tolerance subsequent to weight loss. DESIGN: Forty-six nondiabetic, obese [mean (+/-SEM) body mass index (in kg/m(2)): 31.2 +/- 0.3] men (n = 20) and premenopausal women (n = 26) aged 28.0 +/- 0.7 y were randomly assigned to 1 of 3 diets after > or = 8% weight loss: 1) MUFA diet (n = 16): moderate in fat (35-45% of energy) and high in monounsaturated fatty acids ( > 20% of energy); 2) LF diet (n = 18): low-fat diet (20-30% of energy), and 3) control diet (n = 12): 35% of energy as fat ( > 15% of energy as saturated fatty acids). Protein accounted for 15% of energy in all 3 diets. A 2-h oral-glucose-tolerance test (OGTT) was performed before and after the 6-mo dietary intervention. All foods were provided by a purpose-built supermarket. RESULTS: After 6 mo, the MUFA diet reduced fasting glucose (-3.0%), insulin (-9.4%), and the homeostasis model assessment of insulin resistance score (-12.1%). Compared with the MUFA diet, the control diet increased these variables [1.4% (P = 0.014), 21.2% (P = 0.030), and 22.8% (P = 0.015), respectively], as did the LF diet [1.4% (P = 0.090), 13.1% (P = 0.078), and 15.5% (P = 0.095), respectively]. No significant group differences were detected in glucose or insulin concentrations during the OGTT, in the Matsudas index, in body weight, or in body composition. CONCLUSION: A diet high in monounsaturated fat has a more favorable effect on glucose homeostasis than does the typical Western diet in the short term and may also be more beneficial than the official recommended low-fat diet during a period of weight regain subsequent to weight loss.