The initiation and progression of periodontal disease is mediated by various protein and lipid molecules, known as inflammatory mediator, that are released by inflammatory and immune cells in response to the biofilm accumulation on the teeth. It has become clear that it is the host derived enzymes and mediators like matrix metalloproteinases (MMPs), cytokines, and other inflammatory mediators like PGE2 that cause the majority of tissue destruction in the periodontium. Ironically, the same host systems that defend against diverse pathogens are also responsible for tissue destruction. Hence, the spatial orientation of the inflammatory infiltrate to the bone and the periodontal tissue is an important component that can determine whether the destructive influence is predominant over the infection control and therefore role of pro-inflammatory mediators in the process of inflammation is important.