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OBJECTIVE The aim of the study was to identify the possible benefits of physical activity program in improving the antioxidant enzymes activity and lipid profile among smokers. PATIENTS AND METHODS Fifteen cigarette smokers (CS), 14 hookah smokers (HS), and 14 non-smokers (NS) participated in the low-intensity continuous training (LCT). Eleven CS, 12 HS, and 12 NS participated in the moderate-intensity intermittent training (MIT). The LCT groups performed a 20 to 30-minute continuous exercise at 40% of the VO2max. The MIT groups performed 6 to 10 sets of 2-minute sprint at 70% of the VO2max interspersed by a 1-min recovery period. At baseline and after 12 weeks of intervention, the antioxidant defense activity and lipid profile were assessed. RESULTS The improvement in antioxidant capacity under the effect of MIT program is statistically more significant than after LCT. The increase of glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), malondialdehyde (MDA) and α-tocopherol was higher in smoker subjects participating in the MIT program compared to those participating in the LCT. In contrast, the LCT program has favorably altered lipid and lipoprotein profile of smokers and thus reduced their cardiovascular risk. CONCLUSIONS The combination of the two training methods may have major implications in both defense and prevention programs.