Physical activity (PA) is beneficial to overall health, in part due to physiological changes that lower risk factors for cardiovascular disease, including reduced inflammation. However, the mechanism by which PA reduces inflammation is unclear. One possible pathway is that PA improves body composition which in turn reduces inflammation. To test this hypothesis, we used structural equation modeling (SEM) to assess PA-body composition -inflammation pathways, as well as influences of age. In a sample of 72 healthy males with a range of PA profiles (age 18-65, mean ± sd = ), we measured PA as metabolic equivalent tasks (as per the International PA Questionnaire), body composition as percent body fat, lean mass, and fat mass, and inflammation as plasma interleukin-6 (IL-6). We treated body composition in the SEM analysis as a latent variable indicated by the three measures. We performed statistical corrections for missing values and one outlier. The model demonstrated significant effects of PA on IL-6 both directly and through body composition. Percent body fat, fat mass, and lean mass were significant indicators of the body composition latent variable. Additionally, age showed an indirect effect on IL-6 through body composition, but no direct effect. The findings suggest that PA does improve inflammatory profile through improving body composition, but that other pathways also exist.