© 2005 Human Kinetics Publishers, Inc. Background: Markers of inflammation are emerging as novel indices of cardiovascular risk. These markers have been shown to alter acutely after intense exercise; however, the effects of more moderate intensity exercise in healthy individuals is not known. Walking forms a cornerstone of physical activity promotion, so the inflammatory response to this exercise merits investigation. This study evaluated the effects of a 45-min walk on C-reactive protein (CRP) and interleukin 6 (IL-6), in sedentary, overweight men. Methods: Fifteen men (49.7 ± 5.9 y) walked for 45 min at 60 to 70% of predicted maximum heart rate. Fasted blood samples were taken prior to and immediately 1 hr and 24 h post-walk. Results: IL-6 decreased from 1 h post-walk to 24 h post-walk (P < 0.01). No significant changes were observed in CRP. Conclusions: These findings suggest that 45 min walking at 60 to 70% HRmax-p causes a decrease in IL-6 24 h post-exercise, but does not evoke a significant response in CRP levels.