Objectives/Methods. NOS-activation in erythrocytes (eryNOS) of patients suffering from type 2 diabetes is impaired. The present study investigated whether physical exercise (bicycle ergometry, WHO-scheme) may influence eryNOS activation (immunohistochemical detection of eryNOS phosphorylation at serine 1177) and whether this process may be altered due to a six week hypoxia interval training (4x/week à 90 min: 3x25 min. with an interruption of 5 min. at 15.4% O2 (first week), 14.5 % O2 (second week), 12.7 %O2 (last 4 weeks); support by Höhenbalance GmbH, Cologne, Germany) in men suffering from non-insulin-dependent type 2 diabetes (NIDDM, n=7, age: 61.6+/­10 yrs, BMI: 32.1+/­6.2 kg/cm²). Vascular elasticity (TensioClinic Arteriograph, TensioMed Ltd., Budapest, Hungary) and basal erythropoietin plasma concentrations (ELISA) were measured as well. Results. Before the hypoxia-intervention, eryNOS phosphorylation at serine 1177 did not change during a cycling ergometric test and 30 min. thereafter (eryNOS- pSer1177, basal: 17.4+/­12.0 arbitrary grey values (arGV) vs. exercise: 8.4+/­9.2 arGV vs. 30 min. after exercise: 8.9+/­7.2 arGV). The 6- weeks-hypoxia intervention significantly decreased basal eryNOS-pSer1177 (2.2+/­2.5 arGV). In contrast to the situation before, a significant increase in eryNOS-pSer1177 was now observed after bicycle ergometry (7.6+/­3.0 arGV) and a decrease to basal values 30 minutes after the ergometer testing (3.8+/­1.5 arGV). The alterations of exercise-dependent eryNOS Ser1177 phosphorylation were independent from exercise-induced blood pressure alterations, alterations of small artery elasticity and basal erythropoietin plasma concentrations. Conclusions. Exercise-dependent eNOS phosphorylation at serine 1177 is altered in NIDDM and may be restored by a six week intermittent hypoxia training. The underlying mechanisms seem to be independent from blood pressure alterations, alterations of small arteries elasticity and basal erythropoietin plasma concentration.