Diabetes mellitus (DM) is accompanied by increased formation of free radicals and decreased antioxidant capacity, leading to oxidative stress. Current management of DM includes physical activity, but the impact of prolonged exercise on oxidative stress is unclear. We investigated the oxidative stress during prolonged moderate exercise in a group of insulin-dependent patients and a group of well-matched healthy controls. Nine patients (47±10 years, 73±15 kg, 170±10 cm; Hba1c 7.1±1.1%) and 15 controls (46±10 years, 75±16 kg, 174±10 cm) performed a 3-hrs constant intensity walk at 30% of their heart rate reserve. Patients were given appropriate amounts of sucrose to avoid hypoglycemia. Venous blood samples were obtained prior to and after the walks to determine glucose and insulin levels. The FORT test (Callegari1930, Italy) was performed on capillary blood at the start and thereafter at 30 min intervals. Glucose and insulin levels were higher in patients than in controls (p<0.05 both prior to and after the exercise). Patients showed higher oxidative stress values as compared to healthy controls (380.1±14.7 vs. 293.1±9.6 a.u.; p<0.05). Oxidative stress remained constant in both groups throughout the exercise (p=NS). In conclusion, even if patients usually show higher oxidative stress values than healthy people, prolonged moderate exercise does not exacerbate this potentially harmful condition.