Insulin resistance is a major factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and is related to the fatty acid profile of the plasma membranes. The purpose of the present study was to investigate fatty acid composition and cholesterol content of cell membranes in patients with type 2 diabetes and, thus, to evaluate the possible factors leading to the alteration of plasma membrane fluidity. The study was performed in 20 healthy control subjects and 32 patients with type 2 diabetes. The fatty acid profiles and cholesterol content of the erythrocyte (RBC) and leukocyte (WBC) membranes were determined by a gas chromatographic method. When one considers the membrane constituents increasing fluidity and the ones decreasing it, the diabetics had a membrane composition decreasing fluidity compared to controls. On the other hand, when compared to control subjects, type 2 diabetic patients showed a significantly higher proportion of C16:0 components in erythrocyte and leukocyte membranes and plasma samples (25.4+/-3.1% vs. 31.1+/-4%; 23.3+/-2.4% vs. 29.3+/-5.2%; 27.6+/-3.9% vs. 34.5+/-5.7%; p<0.005, p<0.01 and p<0.005, respectively). Our results suggest that the ratio of saturated:unsaturated fatty acids changes in plasma and cell membranes of patients with type 2 diabetes. This situation may cause, at least in part, RBC-WBC function abnormalities and insulin resistance because of inconvenient membrane fluidity.