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Objective: Inflammation plays a major role in the pathogenesis of atherosclerosis. Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue. The aim of this study is to investigate changes in the inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) during weight reduction with orlistat treatment in obese patients., Methods and Results: Thirty-six obese (BMI: 36.1 +/- 3.4 kg/m2) and II non-obese (BMI: 22.9 +/- 1.7 kg/m2) subjects were studied. IL-6 and hs-CRP levels were evaluated at baseline. In obese subjects after treatment of orlistat 120 mg three times daily for 6 months, IL-6 and hs-CRP levels were repeated. Levels of circulating IL-6 (p < 0.05) and hs-CRP (p < 0.01) were significantly higher in the obese group than in the non-obese group. Plasma IL-6 (r = 0.29 and p < 0.05) and CRP (r = 0.35 and p < 0.05) concentrations correlated positively with the level of obesity assessed by BMI at baseline. After 6 months of orlistat treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Compared with baseline, weight loss was associated with significant reductions of IL-6 (p < 0.001) and hs-CRP (p < 0.001) levels., Conclusion: In summary plasma IL-6 and hs-CRP levels were increased in obese patients. Orlistat-induced weight reduction was associated with decreasing levels of both IL-6 and hs-CRP in obese subjects. Because inflammatory mediators may be directly involved in atherogenesis, this would suggest that interventions to reduce IL-6 and CRP levels could be cardioprotective.