Background: It has recently been suggested that skeletal muscle has an important role in insulin resistance in obesity, in addition to exercise tolerance and the fat index. The aim of this study was to identify body composition factors that contribute to improve-ment of insulin resistance in female patients with obesity who reduce body weight. Methods: We studied 92 female obese patients (age 40.9±10.4 years, body mass index 33.2±4.6 kg/m²) who reduced body weight by ≥5% after an intervention program including diet, exercise therapy, and cognitive behavioral therapy. Before and after the intervention, body composition was evaluated by dual-energy X-ray absorptiometry to examine changes in skeletal muscle mass. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured as an index of insulin resistance. Cardio-pulmonary exercise was also performed by all patients. Results: There were significant improvements in body weight (-10.3%±4.5%), exercise tolerance (anaerobic threshold oxygen uptake 9.1%±18.4%, peak oxygen uptake 11.0%±14.2%), and HOMA-IR (-20.2%±38.3%). Regarding body composition, there were significant decreases in total body fat (-19.3%±9.6%), total fat-free mass (-2.7%±4.3%), and % body fat (-10.1%±7.5%), whereas % skeletal muscle significantly increased (8.9%±7.2%). In stepwise multiple linear regression analysis with change in HOMA-IR as the dependent variable, the change in % skeletal muscle was identified as an independent predictor (β=-0.280, R2=0.068, P<0.01). Conclusion: Improvement of insulin resistance in female obese patients requires maintenance of skeletal muscle mass.