Background. Orthodontic tooth movement (OTM) occurs in the alveolar bone; therefore, any condition affecting bone quality can alter OTM. This study aimed to evaluate the effect of amitriptyline on OTM in rats. Methods. Forty-five male Wistar rats were randomly divided into three groups: (I) no injection, (II) injection with saline solution, and (III) injection of amitriptyline. Next, a 60-gr force was applied to the maxillary left first molar tooth of all the rats, using a nickel‒titanium closed-coil spring ligated between the maxillary incisors and the left first molar tooth. The rats were sacrificed after 21 days to measure OTM and perform histological analysis to determine the number, width, and depth of resorptive lacunae, osteoclast counts, and periodontal ligament (PDL) width. Results. The highest and the lowest OTM rates were found in the control and amitriptyline groups, respectively; however, there was no significant difference between the study groups in this regard. Histological analysis showed a significantly lower number of resorption lacunae in the amitriptyline group than the saline group. Conclusion. Although no significant difference was noted in OTM after amitriptyline administration, a reduction in the number of resorptive lacunae in rats injected with amitriptyline suggests that amitriptyline affects the bone tissue at the cellular level., (©2020 The Author(s).)