OBJECTIVE To investigate whether the improvement in insulin resistance by weight loss is associated with changes in skeletal muscle fiber composition or capillary density. METHODS Longitudinal, clinical intervention study of a 2.1 MJ diet daily for 3 weeks and 3.4 MJ diet daily for 9 weeks. METHODS Seven obese (age: 41-59 y, five men, BMI > 34 kg/m2) non-diabetic subjects. METHODS Insulin action was measured by the euglycaemic hyperinsulinaemic clamp before and after 3 and 12 weeks of the very low calorie diet. In addition, the skeletal muscle biopsies were taken before and after the 12 weeks. RESULTS During the 12 weeks, the subjects lost about 16% of body weight. The weight loss was accompanied by a nearly two-fold increase in total body glucose disposal rate (GDR; baseline vs 12 weeks: 842 +/- 91 vs 1505 +/- 242 mu mol/m2/min; p < 0.05). Most marked improvement was observed in non-oxidative component of GDR, which increased 2.7-fold as compared to baseline (292 +/- 113 vs 788 +/- 231 mu mol/m2/min; p < 0.05). However, no significant change in proportion of type II fibers as well as in skeletal muscle capillary density occurred during the study. CONCLUSIONS In obese non-diabetic subjects the improvement in insulin sensitivity induced by weight loss was not accompanied by marked changes in skeletal muscle fiber composition or capillary density. However, due to small number of subjects studied, the role of structural changes in the muscle fiber composition cannot be entirely ruled out.