The involvement of glutathione in the response of skeletal muscle following repetitive, high-intensity mechanical loading is not known. We examined the influence of a glutathione antagonist [l-Buthionine Sulfoximine (BSO)] had on the adaptability of skeletal muscle during chronic mechanical loading via stretch-shortening contractions (SSCs) in young and old rats. Left dorsiflexor muscles of young (12 weeks, N = 16) and old (30 months, N = 16), vehicle- and BSO-treated rats were exposed three times per week for 4.5-weeks to a protocol of 80 maximal SSCs per exposure in vivo. Skeletal muscle response to the SSC exposure was characterized by muscle performance, as well as muscle wet-weight and quantitative morphological analyses following the exposure period. Results reveal that generally, muscle performance increased in the young rats only following chronic SSC exposure. BSO treatment had no effect on muscle performance or morphology following the chronic SSC exposure in old rats. Muscle wet-weight was increased following exposure compared with the contra-lateral control limb, irrespective of age (p < 0.05). Muscle cross-sectional area increased approximately 20% with SSC loading in the young, vehicle rats, while increasing approximately 10% with SSC loading in old, vehicle rats compared with control rat muscle. No degenerative myofibers were noted in either age group, but edema were increased as a result of aging (p < 0.05). We conclude that our results indicate that glutathione depletion does not adversely affect muscle performance or morphology in old rats. Nevertheless, we continue to show that aging negatively influences performance and morphology following chronic SSC exposure.