Background: Circulating soluble transferrin receptor (sTfR) has been recently found to be associated negatively with insulin sensitivity. Objective: To evaluate circulating sTfR concentration after changing insulin sensitivity in obese individuals. Design: Circulating sTfR concentration was evaluated after diet-induced weight loss in obese women (diet (D) group, n ¼ 8); after diet-induced weight loss plus resistance training (D þ RT group, n ¼ 11); and after follow-up without weight loss (control (C) group, n ¼ 7). Results: After 16 weeks, insulin sensitivity (HOMA (Homeostasis Model Assessment) value) significantly improved in parallel to weight loss (À7.3%) and reduced total fat mass (evaluated using magnetic resonance imaging) in the D group. Thigh muscle mass decreased significantly (P ¼ 0.03). Serum sTfR concentration did not change significantly. In the D þ RT group, weight loss (À8.7%) and improvement of insulin sensitivity were of similar magnitude. Thigh muscle mass was preserved (P ¼ 0.8). Serum sTfR concentration decreased significantly (P ¼ 0.001). Interestingly, higher the thigh muscle volume after weight loss, higher the decrease in circulating sTfR concentration. We also found that higher the increases in leg force at week 16, higher the decrease in circulating sTfR concentration in all individuals as a whole. No significant changes were observed in insulin sensitivity, sTfR concentration or thigh muscle mass in the C group. Conclusion: These findings suggest a long-term regulation of serum sTfR concentration by exercise-induced improvement of insulin sensitivity in obese individuals.