Clodronate, a non-N-containing bisphosphonate, strongly inhibits bone resorption and also has anti-inflammatory properties. The purpose of this study was to examine the effect of the local administration of clodronate on orthodontic tooth movement. Both the right and left upper first molars of 26 7-week-old male Wistar rats were moved buccally with a standardized expansion spring. Clodronate solution was injected into the sub-periosteum area adjacent to the left upper molar every third day during the experimental period. The right first molar served as the control. Local injection of clodronate caused a significant (P < 0.001) and dose-dependent reduction in tooth movement in the rats. The number of osteoclasts on the clodronate-injected side was significantly less (P < 0.01) than on the control side. Local clodronate also inhibited root resorption incident to tooth movement. These results suggest that localized use of clodronate could be a useful therapeutic adjunct in orthodontic treatment.