Several studies suggest that inflammation plays an important role in the pathogenesis of diabetes mellitus, as well as atherosclerosis, and acute-phase reactants have been proposed as monitors for the ongoing process of these diseases. We studied the clinical significance of serum high-sensitivity C-reactive protein (hs-CRP) in relation to chronic diabetic complications using 114 Japanese patients with Type 2 diabetes mellitus. The hs-CRP values were normalized by logarithmic transformation for statistical analysis. Retinopathy and hypertension were extracted as significant modulators for the hs-CRP value in the diabetic patients, in addition to previously known factors, age, and body mass index (BMI), by multivariate analysis. The hs-CRP level in normotensive diabetic patients without retinopathy was not significantly different from that of normal control participants after adjustment for age and BMI. The hs-CRP value was significantly high in the patients with hypertension, despite the existence or absence of diabetes. On the other hand, the hs-CRP level of the diabetic patients complicated with retinopathy was low especially in those with hypertension. The frequency of patients having an hs-CRP value above 1.0 mg/l who are thought to be at risk for cardiovascular diseases was also high in the patients complicated with hypertension and low in the diabetic patients with retinopathy. These results indicate that the presence or absence of hypertension and retinopathy should be taken into consideration for the interpretation of the serum hs-CRP in diabetic patients.