BACKGROUND Osteoporotic fractures are common in postmenopausal women and associated with complications. Numerous studies have demonstrated that icariin can be used to treat fractures and osteoporosis. Herein, we evaluated the efficacy of gavage-administered icariin to promote fracture healing in postmenopausal osteoporotic fracture (POF) rats. MATERIAL AND METHODS In this study, ovariectomy-induced POF rats were treated with 600 mg/kg icariin. Micro-computed tomography (micro-CT) was used to assess fracture healing; besides, serum APK, TRACP-5b, and E₂ expression levels were detected by commercial kits, and the uterine index was calculated. In addition, the expression of osteogenesis-related proteins (Runx 2 and COL1A2) in the callus was measured by western blot, whereas the expression of OPG/RANKL pathway proteins was measured by western blot and immunohistochemical analysis. RESULTS Our data revealed that icariin promoted the expression level of Runx 2 and COL1A2 and suppressed the expression level of serum bone turn over biomarkers via the OPG/RANKL pathway. Besides, a more mature callus was observed in the POF rats receiving icariin than in the untreated POF rats, while serum E₂ and uterine index were unaffected by icariin treatment. CONCLUSIONS These results revealed that icariin could promote fracture healing in ovariectomized rats via OPG/RANKL signaling, and that serum E₂ and uterine index were not affected by icariin treatment.