It is recognized that the path from physical inactivity and obesity to lifestyle-related diseases involves low-grade inflammation, indicated by elevated plasma levels of inflammatory markers. Interestingly, contracting skeletal muscle is a major source of circulating interleukin-6 (IL-6) in response to acute exercise, but with a markedly lower response in trained subjects. As C-reactive protein (CRP) is induced by IL-6, we hypothesized that basal levels of IL-6 and CRP reflect the degree of regular physical activity when compared with other markers of inflammation associated with lifestyle-related morbidity. Fasting plasma/serum levels of IL-6, IL-18, CRP, tumur necrosis factor-α (TNF-α), soluble TNF receptor II (sTNF-RII), and adiponectin were measured in healthy non-diabetic men and women (n=84). The amount of leisure-time physical activity (LTPA) was assessed by interview. Obesity was associated with elevated insulin, C-peptide, triglycerides, low-density lipoprotein, IL-6, CRP, and adiponectin (all P<0.05). Importantly, physical inactivity was associated with elevated C-peptide (P=0.036), IL-6 (P=0.014), and CRP (P=0.007) independent of obesity, age, gender, and smoking. Furthermore, the LTPA score was inversely associated with IL-6 (P=0.017) and CRP (P=0.005), but with neither of the other markers. The results indicate that low levels of IL-6 and CRP – not IL-18, TNF-α, sTNF-RII, or adiponectin – reflect regular physical activity.