Adiponectin is an adipose tissue-specific protein and plays an important role in insulin sensitivity. On the other hand, intramyocellular lipid content and hepatic lipid content (HLC) are related to insulin resistance in humans. In the present study, the possible relations between the serum concentration of adiponectin and intracellular triglyceride content in skeletal muscle and in the liver were investigated in individuals with type 2 diabetes mellitus. Fifty Japanese sedentary subjects (34 men, 16 women) with type 2 diabetes who had neither been treated with insulin nor with thiazolidinediones were enrolled in the study. Insulin sensitivity in vivo was evaluated by measurement of the glucose infusion rate during a hyperinsulinemic-euglycemic clamp and of the homeostasis model of assessment-insulin resistance index. The intracellular triglyceride content in skeletal muscle and the liver was determined by nuclear magnetic resonance. The serum adiponectin concentration was inversely correlated with both HLC ( r = -0.39, P < .01) and the homeostasis model of assessment-insulin resistance index ( r = -0.32, P < .05), but it was not significantly related to either intramyocellular lipid content or glucose infusion rate during the hyperinsulinemic-euglycemic clamp in individuals with type 2 diabetes. These results suggest that adiponectin might play an important role in the regulation of HLC and basal insulin sensitivity in individuals with type 2 diabetes.