The objective was to examine the effects of repetitive local administration of adiponectin on experimental tooth movement in rats.The maxillary right first molar of male Wistar rats (n=24) was moved mesially for 14days, with local adiponectin injections (0.2 or 2μg) every third day. Micro-computed tomography was performed at days 0, 6 and 14 and molar movement, bone density and bone volume fraction were calculated from the scans. Changes in extracellular matrix collagen and cell numbers in the periodontal ligament were analyzed histologically, and levels of circulating cytokines were measured by Luminex and ELISA.Adiponectin injections induced a reduction in tooth movement after 12 and 14days compared to controls. No tooth movement was observed between days 3 and 14 in the group receiving the highest dosage (2μg) of adiponectin. Differences in bone density and bone volume fractions between treatment and control groups were not identified. Relative size and morphology of collagen fibrils, and cell number in the periodontal region after adiponectin injections were unchanged compared to controls. Levels of circulating adiponectin or other selected factors in plasma were not influenced by the adiponectin injections.Submucosal injections of adiponectin prevented experimental tooth movement in rats. The effect was dosage-dependent and local. Adiponectin injections caused no detectable changes in bone density, periodontal cell number or collagen content.