Objective: To elucidate the effect of bone morphometric changes on orthodontic tooth movement (OTM) in zoledronic acid-treated ovariectomized rats. Materials and Methods: Twenty-one 10-week-old female Wistar rats were divided into ovariectomy (OVX), OVX with zoledronic acid administration (OVX + ZOL), and sham operation (control) groups. Two weeks after OVX, ZOL administration was initiated. Twelve weeks after OVX, a nickel-titanium closed-coil spring of 25-g force was applied mesially to the maxillary left first molar. In vivo micro-computed tomography (CT) of the left proximal tibia was performed for bone morphometric analysis every 2 weeks after OVX. In addition, OTM was investigated using micro-CT at 0, 12, and 14 weeks after OVX. Results: There were significant differences in the bone mineral content (BMC), bone volume (BV), BMC to tissue volume ratio (BMC/TV), and BV to TV ratio of trabecular bone between the control and OVX groups and also between the OVX + ZOL and OVX groups. In the OVX + ZOL group, increased BMC and BV in the cortical bone and increased bone mineral density (BMD) in the trabecular bone were observed. Interestingly, OTM in the OVX group was almost two times more than that in the control and OVX + ZOL groups. Moreover, OTM was correlated with BMD, BMC, BV, and BMC/TV in the trabecular bone. Conclusions: OVX accelerated OTM, while ZOL suppressed it. OTM demonstrated a significant negative relationship with trabecular bone mass. (Angle Orthod. 2013;83:766-773.)