We examined reactive oxygen species as upstream activators of NF-κB and Foxo in skeletal muscle during disuse atrophy. Catalase, an enzyme that degrades H 2 O 2 , was overexpressed in soleus muscles via plasmid injection prior to seven days of hind limb immobilization. The increased catalase activity abolished immobilization-induced transactivation of both NF-κB and Foxo, and it attenuated the loss of muscle mass. Thus, H 2 O 2 may be an important initiator of these signaling pathways which lead to muscle atrophy.