Type 2 diabetes mellitus (T2DM) is associated with an increased release of free radicals which play an important role in the manifestation of diabetes and in the progression of diabetic complications. Peroxiredoxins are thought to be essential components of the erythrocyte antioxidative defense. Therefore, we compared peroxiredoxin isoform contents (PRDX1-6 immuno-histochemial stainings) in the erythrocytes of overweight/obese T2DM men (n = 6) and of BMI-matched non-diabetic male control subjects (n = 6). Only erythrocyte PRDX1 and PRDX2 proteins were detectable using immunohistochemical methods. PRDX1 was significantly increased in T2DM men relative to control subjects (+95.9%, P ≤ 0.05). Furthermore, we studied the influence of a 3-month endurance training program (3 times a week, cycling at 75% maximal heart rate) on erythrocyte PRDX1 and PRDX2 contents in overweight/obese T2DM men (n = 11). Training significantly increased PRDX2 at rest (+96%, P ≤ 0.05). The up-regulation of the peroxiredoxin system may help counteract free radicals in the erythrocytes of T2DM patients.