The purpose of this study was to investigate the effect of chronic moderate-intensity training in order to prevent muscle atrophy with a focus on TNF-α and atrogin-1/MAFbx as main proteolytic indicators. Hindlimb unloading model of mice received treadmill running exercise for 1 hr per day during hindlimb unloading period of 6 weeks. The gastrocnemius muscle mass, muscle fiber cross-sectional area, and succinate dehydrogenase (SDH) activity in the muscle fiber were higher in the exercised group, while TNF-α and atrogin-1/MAFbx mRNA expressions were significantly lower. Results in the present study showed that chronic exercise could prevent over expression of TNF-α and atrogin-1/MAFbx in the atrophied skeletal muscle, providing further support to the effects of chronic exercise training on muscle atrophy.