Objective: This study examined whether yogurt supplementation attenuated the weight gain and insulin resistance in mice fed a moderate-fat diet. Methods: Nine-week-old male mice (F1 BTBR × C57Bl6/J) were housed individually for the duration of the study. After initial measurements of body weight and composition, mice were randomly assigned to receive one of two isocaloric diets (19.4% kcal protein, 45.5% kcal carbohydrate, and 35.1% kcal fat). One diet was supplemented with dried yogurt powder (10.75 g/100 g of diet). In the first experiment, mice received the diets for 4 wk, after which body weight and body composition were reassessed. In the second experiment, an insulin tolerance test was performed at week 4 and glucose uptake in gonadal fat was assessed at week 5. Results: Baseline body weight was not significantly different between control and yogurt mice (P = 0.85). Body weight and fat mass increased significantly over time (P < 0.001) and there was a significant effect of diet on the increase in body weight (P < 0.05) and fat mass (P < 0.001), with the yogurt mice gaining less weight and fat than the control mice. Food intake was not significantly affected by the yogurt supplementation (P = 0.906). Digestive efficiency was significantly lower in the yogurt mice (P < 0.05) due to greater fecal production (P < 0.01). There was no significant effect of diet on the glucose area under the curve during the insulin tolerance test (P = 0.24). Glucose uptake in the gonadal fat was significantly higher in the yogurt mice than in controls under basal (P < 0.05) and insulin-stimulated (P < 0.05) conditions. Conclusion: Yogurt supplementation resulted in less weight and fat gain in mice fed isocaloric diets due to a decrease in digestive efficiency. Yogurt also enhanced the uptake of glucose in fat but did not significantly improve insulin sensitivity. © 2007 Elsevier Inc. All rights reserved.