This study investigated the age effect on antioxidant adaptation to muscle disuse. Adult and old rats were randomized into 4 groups: weight bearing (control), 3 days of hind-limb unloading (HU), 7 days of HU, and 14 days of HU. Activities of Cu-Zn superoxide dismutase (SOD), catalase, and glutathione (GSH), as well as GSH peroxidase levels were measured in the soleus. Neither disuse nor aging changed the activity of Cu-Zn SOD. The old rats had greater GSH peroxidase activity, whereas the activity of catalase had a compensatory increase with disuse, independent of age. Reduced GSH level and total glutathione (tGSH) level had age-related change with disuse. In old rats, the GSH and tGSH levels were lower with disuse, whereas the levels remained stable with disuse in adult rats. The depletion of intracellular GSH and tGSH levels of muscles from aged animals with disuse may make aged muscles more susceptible to oxidative damage.