The purpose of the present study was to investigate the relationship between the neuropeptide calcitonin gene-related peptide-immunoreactive (CGRP-IR) nerves and the differentiation of undifferentiated mesenchymal cells into fibroblast-like cells and odontoblasts during the healing process after a pulpotomy. The first maxillary molars from 56-day-old Wistar rats (n=60) were used. The rats were sacrificed to undergo an immunoelectron microscopic examination at 1, 3, 7, 14, and 28 days, postoperatively. In 1 to 3 postoperative days, numerous unmyelinated degenerated CGRP-IR nerve terminals were observed. In 7 postoperative days, regenerated terminals were found to contain numerous large granular vesicles, small clear vesicles, a few mitochondria and a labeled organelle. Certain terminals were found to be attached with the cell bodies of fibroblast-like cells and their processes at the fibrous matrix layer of the dentin bridge during healing process following a pulpotomy. In 14 to 28 postoperative days, CGRP-IR nerve terminals had come into contact with the differentiating odontoblasts at the odontoblast layer of the dentin bridge. These findings demonstrate strong evidence that CGRP may be related to both the proliferation and cytodifferentiation process as well as to the active function of the renewed odontoblasts in dentin bridge formation.