Osteoporosis is characterized by reduced bone mineral density (BMD) and changes in bone morphometry, which increases the risk of fracture. However, the lack of proper models of significant osteoporosis limits our study of related medications and fracture mechanisms. The objective of this study was to determine whether a combination of ovariectomy (OVX) and glucocorticoid injection was appropriate for establishing an osteoporosis animal model. Female Sprague-Dawley rats were divided into sham, an OVX group, a glucocorticoid injection osteoporosis (GIO) group, and an OVX + GIO group. All animals were sacrificed in their 26th week and their spines and bilateral femurs were harvested and analyzed. Their bone quality elements, including BMD, trabecular bone architecture, and cortical bone thickness were analyzed via micro-CT, and mechanical strength of the spines was measured with a Universal testing machine, TO-101G. Femur neck and total femur mean BMD (g/cm2) in the OVX + GIO group (0.307, 0.439) was significantly lower than the sham group (0.518, 0.644) and the GIO group (0.485, 0.587). Femur neck cortical bone thickness (cm) in OVX + GIO group (0.369) were significantly less than those in the OVX group (0.421) or the GIO group (0.510). Furthermore, the OVX + GIO group had significantly lower mechanical strength than the other groups in the spine. In conclusion, OVX combined glucocorticoid injection could induce significant bone loss that had poorer bone quality and less mechanical strength than simple OVX or glucocorticoid injection had, without significantly increased mortality. Therefore, OVX + GIO might be an appropriate osteoporosis animal model.