OBJECTIVE - Adiponectin, synthesized in the adipose tissue, appears to play an important role in hyperglycemia and dyslipidemia, as well as in inflammatory mechanisms, which lead to a markedly increased atherosclerotic risk in diabetic subjects. However, previous studies did not evaluate the complex relationships between adiponectin and the array of metabolic abnormalities commonly observed in diabetes. RESEARCH DESIGN AND METHODS - To examine the associations between plasma levels of adiponectin and HbA1c, blood lipids, and inflammatory markers, we obtained blood samples from 741 participants in the Health Professionals Follow-up Study with a diagnosis of type 2 diabetes. RESULTS - Plasma adiponectin levels were positively correlated with HDL cholesterol and negatively correlated with triglycerides, apolipoprotein B-100 (apoB100), C-reactive protein (CRP), and fibrinogen. These associations were not appreciably altered after controlling for lifestyle exposures, medical conditions, and obesity-associated variables. A 10-μg/ml higher level of plasma adiponectin was associated with lower HbA1c (-0.21% points, P = 0.001), triglycerides(-0.39 mmol/l, P < 0.001), apoB 100 (-0.04 g/l, P < 0.001), CRP(-0.51 mg/l, P = 0.003), and fibrinogen (-0.53 μmol/l, P < 0.001) and higher HDL cholesterol (0.13 mmol/l, P < 0.001). Associations between adiponectin and inflammatory markers were furthermore independent of HbA1c and HDL cholesterol, suggesting that the anti-inflammatory properties of adiponectin are not mediated by potential effects on glycemic control and blood lipids. Our results were consistent among obese and nonobese men. CONCLUSIONS - Our study supports the hypothesis that increased adiponectin levels might be associated with better glycemic control, better lipid profile, and reduced inflammation in diabetic subjects. Measures that increase adiponectin levels might be valuable targets for decreasing the atherosclerotic risk present in diabetes.