We examined the in vitro susceptibility of red blood cell (RBC) lipids to oxidation in type 2 diabetic patients with or without angiopathy. Lipid peroxidation was assessed by quantifying thiobarbituric acid (TBA) reactivity as malondialdehyde (MDA). We also examined the RBC antioxidant status by determining glutathione (GSH) levels. Before in vitro oxidation, RBC MDA levels were significantly higher in both diabetic groups than in the controls (P <.001), and a significant difference was found between the two diabetic groups (P <.05). Alter in vitro treatment of RBCs with hydrogen peroxide, the degree of lipid peroxidative damage was significantly higher in diabetic patients with angiopathy versus diabetics without angiopathy (P <.001). Diabetic patients have low RBC GSH levels compared with controls, and after in vitro oxidation, the levels were significantly decreased in diabetics (P <.001). There was not a significant correlation between RBC MDA levels and glycated hemoglobin (GHb), plasma cholesterol, and triglyceride. The correlation between RBC MDA and GSH was weak (P <.001). We suggest that the results of this study might help to clarify the role of oxidative mechanisms as an in vitro model of degenerative damage in type 2 diabetic angiopathic complications. Copyright (C) 1999 by W.B. Saunders Company.