Introduction: The purpose of this study was to determine the response of some immune and inflammatory markers of cardiovascular disease to a single, short intense duration of exrcise, in prepubertal overweight boys exercise. Materials and Methods: To do this, 13 students 11-14 years-old were selected randomly from among voluntary subjects. In the preliminary session VO2max (26.9±4.9 ml/kg/min), weight (77.07±17.33 kg), height (1.65±0.08), fat percent (31.7±5.6 percent), percent), body composition, BMI (28.9±3.5 kg/m2), skeletal age (12.4±0.9 years) with X-ray, pubertal age with Tanner-stage (T3, T4) was measured and determined familiar illness was done four day before experimental session. In the experimental session, firstly, pre-exercise blood sample collected in fasted state, and then every subject on the ergometer cycle started cycling with 65-70% VO2max for 40 min, post 5 min warming, with 5 min cool down at the end of the program. Immediately post-exercise and recovery blood samples were drawn for measurement of plasma leukocyte, C-reaction protein and IL-6. Plasma CBC and its subgroups were measured by a cell counter employing Isotone Soluble technique, while for hs-CRP and IL_6, we used the immunometric assay Eliza kit. Data were analyzed using the analysis of variance with repeated measures (R-ANOVA) test. Results: The results showed there was a significant relation between different blood samplings. The post hoc (LSD) test that showed neutrophils count and hs-CRP and IL-6 levels one hour after exercise statistically was more than pre-exercise (p=0.001, 0.01, 0.01, respectively) also lymphocyte, monocytes, neutrophils counts and IL-6 level immediately post- exercise (p=0.05, 0.01, 0.004, 0.01, respectively). Exercise may initiate the response of inflammatory and immune factors in prepubertal obese boys, and increase levels of these factors. Conclusion: This study indicates that a single intense bout of exercise with 65-70% Vo2max can increase subgroups of with blood cells, C-reactive protein and IL-6 in immature obese and overweight children, intense exercise can be activate immune and inflammatory system and increase levels of some of the cited factors.