 The thiazolidinediones TZD are a class of drugs approved for the treatment of patients with type 2 diabetes mellitus DM; they belong to the family of drugs that activate the peroxisome proliferator-activated receptor-gamma PPAR-gamma. They have been proposed to have strong anti-atherogenic and anti-inflammatory effects even in patients without diabetes. Recent work from our group and others indicates that TZDs significantly improve vascular damage, dysfunction of blood vessels and disease activity in mouse models of lupus and abrogate atherosclerosis. We recently identified the TZD pioglitazone as an effective drug in modulation of vascular function and disease activity in patients with rheumatoid arthritis. In addition, we have found in mouse models of lupus and in in vitro experiments with human lupus cells, that pioglitazone has important roles in modulating immune function and vascular manifestations. Furthermore, this drug is not immunosuppressive, adding an additional advantage when compared to other medications used in this disease. 