The purpose of this study was to investigate cellular responses of periodontal ligaments during tooth movement. Twenty-eight male Sprague-Dawley rats, weighing 200-250 g each, were used. To create the orthodontic force, elastic rubber blocks (0.65 mm thick) were inserted between the maxillary first and second molars on both sides. On days 3, 7, 10, 14, 21 and 28 after rubber block insertion, histopathological changes in both the tension and the pressure sides were examined by immunohistochemistry using proliferating cell nuclear antigen (PCNA) and by the TUNEL method. The ratios of PCNA-positive cells on the tension side 3 and 7 days after rubber block insertion were higher than those on the pressure side. The ratios of PCNA-positive cells on the tension side were highest at day 3 after insertion and then decreased during the remainder of the experimental period. On the pressure side, the ratios of PCNA-positive cells increased up to day 10 post insertion, then decreased from 14 to 28 days. The ratios of TUNEL-positive cells on both the tension and the pressure sides increased throughout the entire experimental period. These results indicate that the periodontal ligaments on the tension side are able to respond more promptly to orthodontic forces than those on the pressure side. The data also suggest that the ratios of cell proliferation and of cell death are closely related to the regeneration and reconstruction of periodontal ligaments which reflect the orthodontic force.