The purpose of this study was to investigate the ability of mechanotherapy to enhance recovery or prevent loss of muscle size with disuse in female rats. Female F344/BN rats were assigned to weight bearing (WB), hindlimb suspended (HS) for 14 days with reambulation for 7 days without mechanotherapy or reambulation (RA) with mechanotherapy (RAM) (study 1), or to WB, HS for 7 days, with HS mechanotherapy (HSM) or without mechanotherapy (study 2) to gastrocnemius muscle. Muscle fiber cross-sectional area (CSA) and fiber type, collagen, satellite cell number, and protein synthesis (k syn ) and degradation (k deg ) were assessed. Study 1: muscle weight, but not CSA, was higher in RAM compared with HS, but CSA was higher in RA compared with HS. Myofibrillar k syn was higher in RA and RAM compared to WB and HS but not different between RA and RAM. Myofibrillar k deg was lower with mechanotherapy compared to HS. Study 2: muscle weight, CSA, and myofibrillar k syn and k deg were not different with mechanotherapy. Collagen content was lower with mechanotherapy but collagen k syn was not. Mechanotherapy was not associated with changes in fiber type, satellite cell, or myonuclear number in either study. Compared to males, female rats had less muscle loss with HS, which was associated with less loss of myofibrillar k syn . Recovery from atrophy was associated with higher k syn in female and lower k deg in male rats. Female rat muscles do not exhibit a growth response to mechanotherapy with disuse or reambulation. Furthermore, male and female rats show distinct responses to different mechanical stimuli.