Dental implant treatment is one of the superior treatment modalities of occlusal rehabilitation. Based on the concept of top-down treatment, guided bone regeneration (GBR) has been reported to be required in more than half cases of implant placement. Recently, various types of biomaterials including bovine bone, β-TCP, and carbonate apatite have been applied as bone graft substitute. However, it is challenging to predict their outcome in augmented bone volume clinically, indicating that there is still no bone substitute materials that are superior to autogenous bone. Although various studies have been conducted on peri-implant bone, it is still unknown how the artificial bone aids in achieving osseointegration. This study aimed to investigate the mechanism of how artificial bone substitute material being replaced by host bone in GBR procedure.Male 6-week-old Wistar rats were used in this experiment. The maxillary right first molar was extracted, and a bone defect was created on the buccal side. After placing an implant into the extraction site, different bone substitute materials, namely bovine bone, β-TCP, and carbonate apatite were used to fill the buccal bone defect, respectively. The grafting site were sutured and allowed to heal for 2 weeks before euthanasia. The maxillae were dissected. Microcomputed tomography (microCT), histological and immunohistochemical analyses were carried out to detect osteoclasts, osteoblasts, neovascularization, and new bone around the implant threads.