Increased concentrations of the marker of inflammation, C-reactive protein (CRP), are associated with insulin resistance, Type 2 diabetes and the development of cardiovascular disease. In particular, inflammation is closely associated with endothelial dysfunction and is recognized as one of the cardiovascular risk factors clustering in the Insulin Resistance Syndrome or Metabolic Syndrome. The exact mechanisms linking insulin resistance and inflammation remain unclear. However, the close association between insulin resistance and inflammation in atherogenesis suggests that therapies that address both parameters may have benefits in reducing diabetes-related macrovascular complications. The thiazolidinedione class of oral anti-diabetic agents are powerful insulin sensitizers that also have anti-inflammatory properties. Treatment with these agents has a range of anti-atherogenic effects, including reduced levels of CRP, plasminogen activator inhibitor-1 (PAI-1), TNF-α and reactive oxygen species. Additionally, the insulin-sensitizing effect of thiazolidinediones improves other factors of the Insulin Resistance Syndrome, including dyslipidaemia and hypertension. Outcome studies are underway to determine if the effects of improving insulin sensitivity and reducing inflammation will translate into clinical benefits and reduce the cardiovascular morbidity and mortality associated with insulin resistance and Type 2 diabetes.