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Introduction: Obesity is characterized by a chronic-low grade inflammation and aberrant regulation of various forms of stress response in key metabolic sites. The white adipose tissue has been identified as the predominant site of obesity-associated inflammatory reactions, which are triggered as a consequence of immune cells infiltration. Physical exercise has been widely recognized for treating obesity and metabolic syndromes. The objectives of this study are: (1) To investigate the release pattern of pro- and anti-inflammatory mediators in obese participants, (2) To evaluate the effect of a defined exercise protocol on their release into the circulation, (3) To correlate their expression with the metabolic and stress markers. Methods: A total of 600 healthy individuals divided into 3 groups using the body mass index as a reference (lean, overweight and obese) are being enrolled in a 6-month defined exercise protocol. Blood samples and abdominal subcutaneous adipose biopsies are collected at baseline (t0) and after 3 (t3) and 6 (t6) months of exercise. Plasma cytokine and metabolic markers levels were assessed simultaneously using the xMAP multiplex immunobead assay technology (Bioplex). Markers of the oxidative stress, namely ROS and TBARS were measured on plasma or serum using commercially available kits. Gene expression profile was done by RT-PCR using RT-profiler- array kits consisting of the heat shock protein panel, obesity panel and the oxidative stress panel. Western blotting and immunohistochemistry techniques were used to validate the gene expression data. Statistical analyses were performed using SAS software. Results: The analysis carried out on a first set of samples indicated significant release of RANTES in obese individuals compared to lean participants (P <0.001). After 3months of regular exercise, level of RANTES in overall obese population was comparable to that of lean category, suggesting that exercise may antagonize obesity-mediated release of RANTES. High release of RANTES in obese individuals is positively correlated with insulin, leptin and TBARS levels. By contrast, we found a negative correlation between RANTES and Hsp-40 expression. Conclusion: Our result demonstrated a differential expression of RANTES chemokine in obese participants in comparison to lean control and highlighted its roles in obesity. Exercise was able to restore the normal expression of RANTES. The existence of a negative correlation between RANTES expression and the metabolic and stress responses is suggestive of a pathological role of RANTES and may be considered a potential therapeutic target. [Copyright &y& Elsevier]