The purpose of this study was to determine the effect of exercise training on the levels of C-reactive protein (CRP) and adiponectin, and to assess whether exercise-induced changes in insulin resistance could be explained in part by changes in these inflammation markers. Study participants included 51 middle-aged (45.3+/-8.3 years; mean+/-SD), overweight (33.7+/-4.8 BMI), insulin-resistant, nondiabetic individuals. Subjects had their insulin sensitivity, body fat, CRP, and adiponectin levels measured, and their predicted maximal fitness calculated before and after 16 weeks of moderate, intense, or no exercise training. Modest improvements in fitness, body composition, and insulin sensitivity were observed, but these changes were not associated with decreased CRP or increased adiponectin levels, even when subjects were stratified by their change in fitness or obesity. Regression analysis demonstrated that the change in percentage of body fat was significantly related to changes in insulin sensitivity, whereas changes in VO2 MAX, CRP, and adiponectin were not. Participation in moderate to intense exercise was not associated with improved measures of chronic inflammation markers, as measured by CRP and adiponectin. Moreover, improvements in insulin sensitivity resulting from exercise or modest weight loss did not appear to be related to changes in these markers.