Background: It is generally believed that exercise is good for health. Exercise can be harmful to immune system depending on type and duration. So it was decided to study the plasma levels of cytokines with increasing severity of exercise. We observed plasma levels of cytokines on performing graded exercise. Cytokines are protein molecules modulating the Immune system. Interferon Gamma and Tumour Necrosis Factor alpha are proinflammatory and anti-inflammatory cytokines respectively. Methods: Study design: Effect of single bout each of moderate exercise and strenuous exercise and one month of regular moderate exercise on plasma TNF- α and IFN-ï§ was assessed. Blood samples were drawn from each subject soon after one bout of moderate exercise. Another blood sample was drawn from each of the subjects after one bout of strenuous exercise which was performed on next day. The third blood sample was drawn on last day of one month of regular moderate exercise after performing the exercise. Subjects consisted of 18 healthy volunteers (10 males and 8 females) with mean age, 20.94 years, range, 18-25 years. The sample size was calculated statistically based on a previous study. TNF- α and IFN-ï§ were estimated by Sandwich ELISA technique. Friedman test was used for analyzing TNF-α and IFN-ï§ values. Results: Mean and SD values of IFN-ï§ and TNF-α (in pictograms per ml) for baseline (no exercise) was: 54.56 ± 28.54 and 26.17 ± 17.62 respectively, for acute moderate exercise: 28.72 ± 27.57 and 53.83 ± 27.25 respectively, for acute strenuous exercise: 20.36 ± 16.96 and 93.50 ± 5.39 respectively and after one month of regular moderate exercise: 106.33 ± 21.51 and 15.61 ± 8.89 respectively. TNF-α and IFN-ï§showed overall significance between different grades of exercise (p < 0.05). Conclusions: Plasma TNF-α increases with one bout of acute moderate exercise and increases further with one bout of acute strenuous exercise and decreases to below baseline values at the end of one month of regular moderate exercise. IFN-ï§levels exhibit opposite behaviour. This shows that regular moderate exercise has beneficial effects on health by way of increasing plasma IFN-ï§ level and decreasing TNF-α level.