BACGROUND: In postmenopausal osteoporosis, hormonal alteration leads to bone turnover and muscle weakness. Activin type IIB receptors were revealed to increase bone & muscle mass. This experiment was designed to explore ActRIIB-Fc-ligands administration alone or with swimming-exercise might restore musculoskeletal system homeostasis followed negative effects of estrogen deficiency in ovariectomized rat model. Materials & Methods: Fifty adult female albino rats were divided into 5groups: Group I (control sham rats) were subjected to i.p. PBS. In the other groups rats were exposed to ovariectomy procedures. Group II, III, IV rats were exposed to i.p. PBS, exercise-training-protocol, i.p. ActRIIB-Fc (5mg/kg/week) 7weeks respectively, while groupV rats were exposed to exercise-training-protocol and i.p ActRIIB-Fc. Finally, body weights & muscle strength tests were examined for all animals. After scarification, uterine weights and muscle mass (quadriceps femoris & gastrocnemius) measurements were obtained. Serum biochemical and histopathological parameters were examined; also, RNA was extracted from their right femora to perform genes expression. Results: Exercise-training and ActRIIB-Fc were capable to reverse changes of muscle strength and bone mass measurements of OVX rats. Significant elevation in osteocalcin & P1NP and significant reduction in CTX, TOS, TAC, IL-1β, IL- 6, and CK values, moreover, down-regulation of RANKL and up-regulation of OPG genes expression were detected. These significant values and histomorphometric osteoporotic variations were more pronounced in groupV. Conclusion: Addition of ActRIIB-Fc ligand to exercise-training-protocol act as a musculoskeletal-enhancing agent in OVX rats. These results were proved by reduction of osteoclast function and elevation of some osteoblast genes expression; therefore, it could be a respectable choice in musculoskeletal disorders management.