ObjectivesThe objective of this study was to determine changes in gene expression by establishing an orthodontic tooth movement (OTM) rat model with appropriate and excessive orthodontic force.Materials and MethodsUsing a closed coil nickel‐titanium spring, the OTM was carried out to apply a mesial force of 50 or 100 g to the maxillary first molars. Micro‐CT, histological and immunohistochemical staining were used to evaluate the bone formation at the tension site and the bone resorption and bone formation at pressure site. Then RNA sequencing and bioinformatic analysis were performed.ResultsAccording to the results of the Mirco‐CT scan of OTM rat models, both the 50 g group and the 100 g group showed variable degrees of reduction in alveolar bone density on the tension and pressure sides. The results of histological and immunohistochemical staining demonstrated that the periodontal tissue and osteogenic ability of the 50 g group were restored at the 14 days, while the 100 g group caused severe periodontal tissue damage. The GO and KEGG analysis results, as well as the number of differentially expressed genes (DEGs), varied depending on the loading time and value of appliance, according to the results of the RNA sequencing. And the immunohistochemical staining results showed that Sfrp4 functioned by efficiently influencing both bone formation and bone absorption.ConclusionsAppropriate orthodontic force value could cause appropriate movement of teeth in rats without adverse periodontal damage. Simultaneously, distinct gene expression patterns were observed at various force levels and time intervals.