INTRODUCTION: Nuclear factor erythroid-2-related factor 2 (Nrf2), is an inducible transcription factor that reduced in type 2 diabetes(T2D) and increases oxidative stress and then stimulating antioxidant expression. The purpose of this RCT was to investigate the effects of HIIT induced H2O2, Nrf2 changes on Glutathione Peroxidase (GPx), Glutathione Reductase (GR), Catalase (CAT) and superoxide dismutase (SOD) in T2D. METHODS: Thirty-three male patients with T2D were randomly divided in 2 groups including to 12-weeks HIIT (10 rotations for 60 seconds (10 x 60s) set in constant watt mode at a pedal cadence of 80 to 100 revolutions/min) or a non-exercise control group. Nrf2, H2O2 and GPx, GR, Cat and SOD protein were measured in response to 12 weeks HIIT. RESULTS: Levels of Nrf2 and H2O2 showed high levels in HIIT with respect to control subjects after 12 weeks' interventions (HIIT). Fasting plasma glucose (FPG) (p = 0.001), postprandial plasma glucose (PPG) (p = 0.001), glycated hemoglobin, (HbA1c) (p = 0.041), plasma total cholesterol (Tc) (p = 0.028), plasma triglyceride (TG) (p = 0.001), Na (p = 0.001), creatine kinase (Ck) (p = 0.035), alkaline phosphatase (ALP) (p = 0.025), hematocrit (Hct) (p = 0.008) and Cortisol (p = 0.001) were statistically significant in the T2D plus HIITgroup. After 12 weeks' interventions (HIIT), control group the Plasma CAT levels (p = 0.001) were found to be higher in HIIT group compared to control group. CONCLUSIONS: Our results provide evidence that HIIT causes an increase in oxidative stress levels, which ultimately the body responds to increased antioxidant levels. Therefore, it is suggested that these indicators (HIIT and H2O2, Nrf2) can be considered as a therapeutic target for type 2 diabetic patients.

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