Interleukin-15 (IL-15) mRNA is constitutively expressed in skeletal muscle. It has hypertrophic and anti-apoptotic roles in vitro but its role in skeletal muscle cells in vivo is unknown. The purpose of this study was to determine if (i) skeletal muscle aging and unloading would alter basal IL-15 expression in skeletal muscle and (ii) the trimeric IL-15 receptor (IL-15R) was expressed in skeletal muscle. Two models of muscle atrophy were used; Hindlimb suspension (HS) in rats and wing weighting in quail for 14 days to induce hypertrophy, followed by unloading for 7 or 14 days to induce muscle atrophy. Aging and HS reduced rat hindlimb muscle mass. IL-15 mRNA was 20% greater in aged vs. young soleus muscles. HS increased soleus IL-15 mRNA by 81% in young rats and plantaris muscle IL-15 mRNA by 71% greater in aged rats. IL-15 had an aging times unloading interaction in rat muscles. Unloading reduced patagialis (PAT) muscle mass in quails. IL-15 mRNA was ~53% greater in control PAT muscles from aged compared to young birds. Following 7 days of unloading, PAT IL-15 mRNA was 25% and 19% greater than control muscles in young and aged birds, respectively. IL-15 mRNA was 16% greater in unloaded compared to control muscles in aged birds after14 days of unloading. Skeletal muscle expressed the mRNA for IL-15R, IL-2/15R-, and c but low levels of IL-2R mRNA. The increase in IL-15 mRNA may be a failed attempt to counteract aging and unloading-induced muscle atrophy in muscles of aged animals.