Periodontal ligament (PDL) is a uniquely differentiated tissue that anchors the tooth to the alveolar bone socket and plays key roles in oral function. PDL cells can respond rapidly to mechanical stimuli, resulting in accelerated tissue remodeling. Cell proliferation is an initial event in tissue remodeling and participates in maintaining the cell supply; therefore, analyzing cell-proliferative activity might provide a comprehensive view of cellular dynamics at the tissue level. In this study, we investigated proliferating cells in mouse molar PDL during orthodontic tooth movement (OTM)-induced tissue remodeling. Our results demonstrated that the mechanical stimuli evoked a dynamic change in the proliferative-cell profile at the entire PDL. Additionally, cell-tracing analysis revealed that the proliferated cells underwent further division and subsequently contributed to tissue remodeling. Moreover, OTM-induced proliferating cells expressed various molecular markers that most likely arise from a wide range of cell types, indicating the lineage plasticity of PDL cells in vivo. Although further studies are required, these findings partially elucidated the global views of the cell trajectory in mouse molar PDL under mechanical-loading conditions, which is vital for understanding the cellular dynamics of the PDL and beneficial for dental treatment in humans.