The purpose of this study was to examine the expression of platelet-derived growth factor C (PDGF-C), which is a new member of the PDGF family, in experimental periapical lesions. Periapical lesions were induced in Sprague-Dawley rats by occlusal pulp exposure in the mandibular first molars. Animals were sacrificed randomly at 0, 7, 14, 21, and 28 days after pulp exposure. Frontal sections were prepared for histological analysis and enzyme histochemistry. Reverse-transcription polymerase chain reaction and immunohistochemistry were performed to detect PDGF-C expression. From day 0 to day 28, PDGF-C messenger RNA were expressed and increased until day 28. A few PDGF-C-positive cells and osteoclasts could be observed on day 7. Both ascended in number on day 14. In the 21- and 28-day samples, the PDGF-C-positive cells increased, whereas fewer osteoclasts were observed. Many of the PDGF-C-positive cells were inflammatory cells with different morphologies. These findings showed that PDGF-C could be observed and might also be involved in the pathogenesis of periapical lesions.