ObjectiveThe present study aimed to investigate the inhibitory effect of acetaminophen on apical root resorption during orthodontic tooth movement by controlling inflammation in the periodontal ligament and apical pulp tissue. MethodsHuman periodontal ligament and pulp cells were subjected to 10 kPa of cyclic tensile force (CTF) in a Flexcell Strain Unit for 48 h. Then, 10 and 100 μM acetaminophen were added to the culture medium, and the expression of interleukin (IL)-1B, receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor (TNF)α, and colony stimulating factor 1 (CSF1) were evaluated. In an animal experiment, the upper first molars of 7-week-old rats were moved mesially by applying 10 g of orthodontic force. After 30 days of force application, the effects of acetaminophen on apical root resorption were examined. ResultsIn both the periodontal ligament and pulp cells, the expression levels of IL-1B, TNFα, RANKL, and CSF1 were significantly higher in the CTF-treated group than in the control group. However, the expression levels of these factors were decreased by acetaminophen administration. High expression of IL-1B, TNFα, RANKL, and CSF1 at the root apex were also detected immunohistochemically in rats after tooth movement, but were decreased by acetaminophen administration. In addition, the number of odontoclasts and the amount of apical root resorption were significantly decreased in the acetaminophen group. Importantly, no significant difference in tooth movement was observed between the acetaminophen and control groups. ConclusionsThese results suggest that acetaminophen can reduce severe root resorption in the apex area without disturbing orthodontic tooth movement.