OBJECTIVES: Moderate weight loss and exercise have been proposed as important tools in the treatment and prevention of type 2 diabetes. Therefore, we tested the hypothesis that short-term (4 weeks) moderate energy restriction (-750 kcal/day) would result in a significant increase in insulin-stimulated glucose disposal (40 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) in moderately overweight postmenopausal women and that when combined with resistance training (RT) an even greater effect would be seen. RESEARCH DESIGN AND METHODS: Older women were randomly assigned to energy restriction (WLoss group; n = 9) or energy restriction plus RT (RT + WLoss group; n = 10). RESULTS: For the WLoss versus the RT + WLoss groups, changes in body weight (-3.0 +/- 0.2 kg vs. -3.2 +/- 0.3 kg), fat mass (FM) (-3.0 +/- 0.3 kg vs. -3.2 +/- 0.3 kg), and percent body fat (BF) (-2.1 +/- 0.4 vs. -2.4 +/- 0.3%) were not different between groups. Muscle mass (group-by-time interaction, P = 0.04) was preserved in RT + WLoss (0.40 +/- 0.40 kg) and reduced in WLoss (-0.64 +/- 0.18 kg). There were no changes in fat-free mass (FFM) and waist-to-hip ratio in either group. Whole body glucose disposal (WLoss 6.14 +/- 0.57 vs. 6.03 +/- 0.53, RT + WLoss 5.85 +/- 0.60 vs. 6.09 +/- 0.56 mg/kg of FFM/min) did not change in either group. CONCLUSIONS: The results of this study demonstrate that short-term energy restriction resulting in moderate decreases in body weight (4.0 +/- 0.3%) and FM (8.2 +/- 0.7%) did not improve insulin-stimulated glucose disposal. The addition of RT to the hypoenergetic diet preserved muscle mass but provided no synergistic effect on insulin action. These results suggest that a greater change in body weight or FM may be necessary to observe a significant improvement in insulin action.