Objective: To test whether oxidative stress could promote a systemic acute-phase response in elderly patients with type II diabetes. Design and Methods: In a group of 30 older diabetic patients with poor glycemic control, serum levels of lipid peroxides, measured as thiobarbituric acid-reacting substances (TBARS); C-reactive protein (CRP); interleukin (IL)-6 and the soluble form of its receptor (sIL-6R), were evaluated at baseline and after 2 and 3 months of therapeutic intervention. Thirty asymptomatic, untreated individuals with abnormal fasting glycemia, but otherwise healthy status, of similar age, sex, and weight served as control group. Results: At baseline, glycemia (8.83 ± 0.67 mmol/l), HbA1C (8.66 ± 0.59%), TBARS (8.68 ± 1.21 µmol/l), CRP (16.05 ± 3.81 mg/l) IL-6 (5.39 ± 1.25 pg/ml) and sIL-6R (1425 ± 492 pg/ml) were significantly higher in diabetic patients than in asymptomatic hyperglycemic individuals (p < 0.001). After treatment, glycemia significantly decreased with respect to baseline values (-9.82% after 60 days and -13.74% after 90 days), as did serum levels of TBARS (-14.05% and -21.89%, respectively), CRP (-32.71 % and -43.86%), IL-6 (-23.75% and -40.63%) and sIL-6R (-34.53% and -48.49%, respectively). In diabetic patients, multiple regression showed, at each time, that TBARS and IL-6 were independently correlated with CRP, considering CRP as the dependent variable. Similar correlations were found in asymptomatic hyperglycemic subjects. Conclusion: These results suggest that oxidative stress might be implicated in promoting a state of low-grade systemic inflammation in elderly patients with type II diabetes.