We examined the proliferative activity, apoptosis, and histogenesis in the early stages of the rat healing socket from just after extraction until new bone formation occurs. Thirty 11week-old male Wistar rats underwent bilateral maxillary first molar tooth extraction. Five craniomaxillary tissue specimens were dissected at the following time points: at 12 h, days 1, 3, 5, 7 and 10 after surgery. The immunohistochemical expression of both proliferating cell nuclear antigen (PCNA) and the Ki67 counterpart of rodent (MIB5) for proliferative activity and both the TUNEL reaction and the immunohistochemical expression of single-strand DNA for apoptosis were evaluated using 6-mu m-thick serial paraffin sections, which were prepared in the coronal plane. The positive cell counts in the socket were converted into the cell numbers per mm 2 as either the proliferative index (PI) or the apoptotic index (AI). The PI and the AI showed maximum levels at 5 days and 12 h after extraction, respectively. The proliferative activity in the early stages of extraction wound healing is initially distributed in the remaining periodontium with load-induced apoptosis, next in the proliferative fibrous tissue, and then around the trabeculae of the new bone marking its peak. Copyright (c) 2007 S. Karger AG, Basel.