High-sensitivity C-reactive protein (CRP) is a novel risk factor for coronary artery disease. It is well known that body weight loss is effective in reducing serum CRP concentration ; however, the effect of exercise training on serum CRP concentration has not been fully elucidated. The purpose of this study was to examine the effect of a 24-week exercise training program on serum CRP concentration in 169 healthy middle-aged and elderly subjects (65.9±6.4 years). Each subject underwent baseline testing (peak oxygen uptake, daily physical activity, body weight, and serum CRP levels), and repeated these tests on completion of the training program. The subjects were classified into 2 groups based on initial CRP levels : normal<1.0 mg/L, n=139, and high≥1.0mg/L, n=30. On completion of the program, both daily physical activity and peak oxygen uptake increased significantly (+33.9±72.4%, p<0.0001, +5.4±14.7%, p=0.014, respectively). However, body weight did not change significantly. In addition, CRP levels of the entire group did not change significantly. However, CRP levels significantly decreased among the high baseline CRP group (from 1.82±0.81 mg/L to 0.98±0.59 mg/L, p<0.0001). It was concluded that serum CRP levels are reduced without body weight loss in response to exercise training in healthy middle-aged and elderly subjects with high initial CRP levels.