Background: This study was to investigate the new mechanism of rosiglitazone in skeletal muscle to improve insulin resistance through relationship between concentrations of adipocytokine and mid thigh low density muscle area. Methods: Forty two type 2 diabetic patients (age: 32~70 years old, BMI 17.48~32.55 kg/m2, 15 women, 27 men) were enrolled in this study, and designed as rosiglitazone 4 mg, administered daily for 12 weeks. We assessed body composition, and measured the level of plasma adiponectin, leptin, resistin and various biochemical parameters. Results: Twelve weeks of 4 mg/day rosiglitazone treatment improved insulin resistance (IR, as measured using the Kitt: from 2.52 0.98 to 2.85 1.11%/min, p<0.05). Plasma adiponectin levels increased from 5.58 2.19 to 8.80 3.02 g/mL (p<0.01). Plasma leptin levels decreased but did not change significantly (7.47 6.44 to 6.63 4.06 pg/mL, p=0.10). Plasma resistin levels decreased from 3.23 2.46 to 1.91 1.93 g/mL (p<0.01). Cross sectional area of low density muscle (LDM) at the mid thigh was positively correlated with insulin resistance. However any concentration of adipocytokines we measured was not associated with insulin resistance in this study. Conclusion: We found that improvement of insulin resistance by rosiglitazone treatment was not associated with change of mid thigh low density muscle and concentrations of adipocytokines. We should consider that our subjects were relatively well obese and their insulin resistance was not severe. We also postulated that other factor rather than accumulation of fatty acid metabolite in skeletal muscle may be much more important in regard to change of insulin resistance with rosiglitazone treatment. It is also possible the effects of rosiglitazone on low density muscle may be different in Korean patients with type 2 DM.