Objective To investigate the effects of local injections of recombinant soluble human receptors on experimental orthodontic tooth movement in the rat. Methods 64 male Sprague- Dawley rats were observed. Starting at day 1, three groups of animals each received local injections of soluble interleukin- 1 receptorⅡ(sIL- 1- RⅡ), soluble tumor necrosis factor receptor Ⅰ(sTNF- RⅠ) and their combinations. One group served as the control. The amount of tooth movement was recorded and selected tissue sections were stained with hematoxylin- eosin(HE) to observe the histological morphologic alterations of the periodontal tissues and also were stained with tartrate- resistant acid phosphatase(TRAP) histochemistry to analyze the changes of the amount and distribution of osteoclasts and odontoclasts. Results The time- depended histomorphology changes in each receptor group were similar to those in the control group, but the resorption of alveolar bone was slighter at each time point and the surface of root appeared no or a few cement resorption signs. On day 14, the TRAP- positive cells on the surface of alveolar bone and root were reduced by approximately 50% relative to those in the control group(P0.05). Conclusion Local injections of recombinant human sIL- 1 - R Ⅱ and sTNF - R Ⅰ in the orthodontic tooth of rats could reduce the amount and velocity of orthodontic tooth movement and reduce the incidence of root resorption.