Abstract： Peri-implantitis (PI) has been defined as an inflammatory lesion of the mucosa surrounding an endosseous implant and with progressive loss of supporting peri-implant bones. In recent years, histopathological differences between PI and periodontitis of natural teeth had been described in animal experiments and a certain number of human experiments. In this paper, we review the histopathological differences between PI and periodontitis reported in the existing literature and try to find the differences in the occurrence and progression of these two diseases. Overall, inflammatory cell infiltrate (ICT) is more extensive in PI than in periodontitis, extending to the alveolar ridge, with dense infiltration of plasma cells, lymphocytes, macrophages, polymorphonuclear leukocytes and a greater number of osteoclasts in the connective tissue, but with less vascular density within ICT than in periodontitis. In addition, foreign bodies are found in PI lesions. The histopathological differences between the two diseases in terms of inflammatory infiltration, vascularity, bone loss, and foreign bodies could partially explain the more rapid progression of PI than periodontitis, suggesting that PI should be taken seriously by physicians. Early diagnosis and treatment are essential to control the progression of PI. In addition, targeted therapy against specific inflammatory cells may become a new direction for PI treatment; reducing titanium particles released into peri-implant tissue by friction or electrochemical corrosion may help to prevent PI.