Increased prevalence of insulin resistance has been observed in patients with rheumatoid arthritis (RA). High-grade systemic inflammation is implicated in the development of insulin resistance in these patients. Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine that plays a role in the initiation and progression of inflammation and the mechanisms associated with accelerated atherosclerosis in RA. In assessing data immediately prior to and after intravenous infusion of the anti-TNF-alpha monoclonal antibody-infliximab in RA patients on period treatment with this drug attributable to disease refractory to conventional disease-modifying antirheumatic drugs, a dramatic improvement of insulin resistance and insulin sensitivity was observed. A long-term positive effect of TNF-alpha antagonists infliximab and etanercept on insulin resistance in RA patients with severe disease was also reported. These results highlight the importance of therapies that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of the metabolic syndrome observed in RA.