It is generally accepted that obesity is associated with many other multiple-risk factor syndromes such as hypertension, hyperlipidemia, type 2 diabetes mellitus, and periodontal disease. The number of obese people is increasing rapidly in both western and eastern countries. Adipocytes in the adipose tissues of obese people produce large quantities of biologically active molecules such as leptin, an important molecule regulating energy expenditure and body weight. Therefore, adipocyte-derived active molecules, named adipocytokines, are candidate molecules accounting for the close association between obesity and other multiple-risk factor syndromes. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is produced by adipocytes, and its blood concentration is elevated in obese patients and declines with weight loss. Studies have demonstrated that TNF-alpha suppresses insulin action via its specific receptor; hence, it exacerbates insulin resistance. In addition to adipocytes, monocytes/macrophages produce large quantities of TNF-alpha. Thus, TNF-alpha, produced from monocytic cells due to inflammatory diseases, may have an additive influence on insulin sensitivity to adipocyte-derived TNF-alpha. Here, we hypothesized that 1) TNF-alpha produced by the adipose tissues of obese patients acts as a risk factor for periodontal inflammation, and 2) TNF-alpha produced due to periodontal inflammation may be an additional important factor influencing insulin sensitivity in both obese and type 2 diabetic patients. We believe that this interaction is a possible mechanism accounting for a 2-way relationship between type 2 diabetes and periodontal disease.