Multiple chemical mediators are constitutively produced from rheumatoid synovium resulting in joint destruction. These include arachidonic acids metabolites such as prostaglandins and leukotrienes, vasoactive amines, kinins, endothelins, complement fragments, reactive oxygens, neutral proteinases and cytokines. Among cytokines, interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor (TNF), platelet-derived growth factor (PDGF), GM-CSF, M-CSF are known to be constitutively produced from inflammatory synovium. Most of these cytokines are mainly produced from synovial cells which are recruited and/or proliferated in the synovium. The mechanism of inducing or aggravating joint destruction with these cytokines and other chemical mediators is discussed.