To investigate the role of plasma cells and macrophages in the development of periapical lesions, we immunohistochemically examined the distribution of these inflammatory cells in experimental induced rat periapical lesions after pulpectomy. The number of ED1-positive mononuclear cells increased rapidly, reached a plateau which remained stable between days 10 and 60, and subsequently decreased. Immunoglobulin (Ig)-bearing plasma cells appeared after 60 days, and, of these, IgG-bearing plasma cells were predominant after 90 days. The radiographic and histopathological findings indicated the development of bone destruction at 10 days which continued until 60 days; tissue repair began to take place after 90 days. The results suggested that macrophages had a close relation to bone destruction and that plasma cells might participate in tissue repair rather than the development of periapical lesions.