The objective of this study was to verify the therapeutic role of mesenchymal stem cells, osteoinductive material or both of them versus calcitonin therapy in betterment of osteoporosis in ovariectomized rat model. Mesenchymal stem cells (MSCs) were harvested from femoral bone marrow and excised from both the omentum and the inguinal fat pad of male rats. Ninety adult female rats were enrolled in the current study and assigned into nine groups: group (1) served as gonad intact control, group (2) served as untreated ovariectomized (OVX) rats, while the groups from the third to ninth were OVX groups treated with, bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue derived mesenchymal stem cells (ASCs), BM-MSCs plus injectable bone substitute (IBS), ASCs plus IBS, IBS, calcitonin and calcitonin plus IBS respectively. BALP gene expression level was detected via real time PCR. In addition, levels of IL-7 in serum as well as level of DPD in urine were determined by ELISA. Moreover, BMD was measured using DEXA technique. The Results showed positive SRY gene expression in the femur bones of the MSCs treated groups, confirming that the intravenously injected MSCs could migrate to the site of injury. MSCs injection with or without IBS reversed the effect of ovariectomy on the studied biomarkers causing significant up-regulation in the expression level of BALP in femur bones and significant reduction in serum, IL-7 and urinary DPD levels. Moreover, the DEXA results revealed that MSCs therapy improved the ovariectomy induced decrease in BMD in some areas of rats' femur bones. In conclusion, the current results indicated the potent role of MSCs in retrieving of osteoporosis. Also, the synergism between MSCs and osteoinductive material could be beneficial for enhancement of the therapeutic effect.