OBJECTIVE: To identify and investigate differences in spinal fusion between the normal and osteopenic spine in a rat model. METHODS: Female Sprague Dawley rats underwent either an ovariectomy (OVX) or sham operation and were randomized into two groups: non-OVX group and OVX group. Eight weeks after OVX, unilateral lumbar spinal fusion was performed using autologous iliac bone. Bone density (BD) was measured 2 days and 8 weeks after fusion surgery. Microcomputed tomography was used to evaluate the process of bone fusion every two weeks for 8 weeks after fusion surgery. The fusion rate, fusion process, and bone volume parameters of fusion bed were compared between the two groups. RESULTS: BD was significantly higher in the non-OVX group than in the OVX group 2 days and 8 weeks after fusion surgery. The fusion rate in the non-OVX group was higher than that in the OVX group 8 weeks after surgery (p=0.044). The bony connection of bone fragments with transverse processes and bone formation between transverse processes in non-OVX group were significantly superior to those of OVX group from 6 weeks after fusion surgery. The compactness and bone maturation of fusion bed in non-OVX were prominent compared with the non-OVX group. CONCLUSION: The fusion rate in OVX group was inferior to non-OVX group at late stage after fusion surgery. Bone maturation of fusion bed in the OVX group was inferior compared with the non-OVX group. Fusion enhancement strategies at early stage may be needed to patients with osteoporosis who need spine fusion surgery.