The purpose of this study was to investigate the effects of bisphosphonate (BP), an inhibitor of bone resorption, on the remodeling of the rat sagittal suture after rapid expansion. Wistar strain male rats were divided into 4 groups and subjected to rapid mechanical expansion with an initial force of 60 g for 3 days. Immediately after the sutural expansion, the appliance was removed in 2 of the groups. In the S group, half of the animals were injected with saline solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. In the B group, half of the animals were injected with bisphosphonate daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. The remaining 2 groups underwent 7 days of mechanical retention before the appliance was removed. In the SR group, half of the animals were injected with saline solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. In the BR group, half of the animals were injected with bisphosphonate solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. The calvariae were fixed in 4% neutral formalin, decalcified, and embedded in paraffin. The amount of relapse and the relevant bone remodeling were evaluated in terms of a relapse ratio and the number of osteoclasts. The relapse ratio was 54.11% in the S group and 32.53% in the B group 7 days after the injection. This ratio was 25.13% in the SR group and 9.60% in the BR group. The number of osteoclasts 3 days after injection was 15.47 in the S group, which was significantly greater than the 5.26 present in the B group. This number was 7.08 in the SR group, which was significantly greater than the 1.83 in the BR group. These results demonstrate that the injection of BP after rapid expansion, if combined with mechanical retention, may produce more secure retention by inhibiting bone resorption, indicating a possibility of employing a pharmaceutical aid to decrease the skeletal relapse after mechanotherapy in clinical orthodontics.