Introduction: Prolonged low-grade inflammation in obesity is associated with excessive oxidative stress and enhances lipid peroxidation. However, few studies have explored the response of inflammatory markers to the combined high protein diet and exercise (HPE) of weight reduction in the adolescent obese population. The objective of this study was to examine the effects of HPE on high-sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA) in the obese adolescent. Methods: The study was an 8-week randomized controlled trial in 56 abdominal obese adolescents (F=47, M=9; aged about 19 to 20 years). The subjects were divided into four groups; high protein and exercise (HPE, n=15), high protein diet (HP, n=15), exercise (E, n=13), and control (C, n=13). The meal diet consisted of 55% carbohydrate, 25%protein and 20%fat. The exercise conducted by circuit training. Body compositions (weight and fat mass) were measured by Bio Impedance Analyzer. hs-CRP and MDA were measured using enzyme-linked immunosorbent assay (ELISA). Results: The change percentage of hs-CRP and MDA were decreased in HPE group by (-23.6±2.9%; -30.9±7.2%), exercise group by (-9.0±4.9%; -9.6±3.2%), HP group by (4.8±2%; -7.3±6.3%) and in the control group (-5±3%) respectively. There was a significant reduced in delta hs-CRP and MDA among four groups (p=0.0001). The change of hs-CRP and MDA were correlated positively with the change in BW and waist circumference (p<0.01). Conclusion: High protein diet and exercise has decreased hs-CRP and MDA levels after weight loss among obese adolescents.