Objective: To observe the effect of different doses of Elcatonin Injection on the prevention of osteochondral osteoporosis in osteoarthritis model rats and the protective effect of articular cartilage. Methods: 32 SPF female Sprague-Dawley rats were randomly divided into 4 groups: control group, model group, low-dose group and high-dose group (8 rats in each group). All groups were established by bilateral anterior cruciate ligament severance (ACLT) and bilateral ovariectomy (OVX), except the control group. The rats in the Elcatonin Injection group were intramuscularly injected with the corresponding dose in the right forelimb once a week: low dose (5 IU/kg) or high dose (10 IU/kg).The control group and the model group were given intramuscular injection of normal saline only. At 12 weeks postoperatively, the biochemical markers of serum bone metabolism (CTX-Ⅰ, CTX-Ⅱ), interleukin (IL-1, IL-6) and tartrate-resistant acid phosphatase (TRACP 5b) were detected. Analysis of subchondral bone changes and full-layer structure of articular cartilage. Results: Compared with the model group, the contents of CTX-Ⅰ, CTX-Ⅱ, IL-1, IL-6 and TRACP 5b were all decreased after the injection of calcitonin, and they were more obvious in the high-dose group (all P＜0.05). However, there was no statistically significant difference between the two groups according to calcitonin (P＞0.05). Compared with the model group, the bone volume fraction (BV/TV), trabecular bone number (Tb.N), and trabecular bone thickness (Tb.Th) of the tibial plateau subchondral bone were increased in the calcitonin group (all P＜0.01, excluding Tb.Th), and the trabecular bone separation (Tb.Sp) decreased (P＜0.01). BV/TV and Tb.N were higher in the high-dose group and lower-dose group (P＜0.05), and Tb.Sp were lower (P＜0.05). The OARSI rating after calcitonin injection was lower in the two groups than in the model group, but the difference was not statistically significant (P＞0.05). Conclusion: Both doses of elcatonin injection can improve bone metabolism and prevent subchondral osteoporosis in osteoarthritis model rats, and can protect articular cartilage, and the high dose performance was better.