Disuse with hindlimb unloading (HU) elicits substantial muscle atrophy, weakness, and inflammation upon reloading. Unloaded skeletal muscle is characterized by oxidative stress and impairment of key stress-response proteins including insulin-like growth factor (IGF-1) and heat shock proteins (HSPs). Recovery of muscle mass following prolonged (28 day) unloading is delayed. The purpose of this study was to determine if IGF-1 and HSP70 signaling were likewise delayed during short-term (7 days) and long-term (28 days) of reloading following long-term unloading in the rat soleus. Twenty-four 6 mo. old Sprague-Dawley rats were divided into four groups: controls, 28 days of HU, HU + 7 days of reloading (HU-R7), and HU + 28 days of reloading (HU-R28). Protein levels of IGF-1, phosphorylated Akt (p-Akt), heat shock factor-1 (HSF-1), HSP70, and 3-nitrotyrosine (3-NT) were assessed by Western immunoblot. IGF-1 protein levels significantly decreased with HU (−62%) and HU-R7 (−67%), and recovered with HU-R28. p-Akt protein levels was markedly increased in HU-R7 (+530%) following HU (+74%) and then recovered after HU-R28. Both HSF-1 and HSP70 levels significantly decreased with HU-R7 (−75% and −71%) and recovered with HU-R28. Our data indicate 2 distinct phases of signaling during reloading: an early phase of reloading characterized by high 3-NT and p-Akt without elevation in IGF-1 and HSP70, and a delayed phase where IGF-1 and HSP70 signaling are elevated.