Aim/hypothesis: The plasma activity of phospholipid transfer protein (PLTP), which has putative pro- and anti-atherogenic roles in lipoprotein metabolism, is increased in type 2 diabetes mellitus. We analysed the relationship between carotid artery intima - media thickness (IMT), an established marker of atherosclerosis, and PLTP activity in diabetic patients and control subjects. Methods: The IMT ( mean of three segments in both carotid arteries by ultrasonography), clinical variables, plasma PLTP activity ( phospholipid vesicle - HDL system), lipoproteins, C-reactive protein and insulin were measured in 87 non-smoking men and women, who had type 2 diabetes mellitus, no cardiovascular disease, and were not on insulin or lipid-lowering medication, and in 83 age-matched control subjects. Results: In diabetic patients, carotid IMT ( p=0.02), pulse pressure ( p= 0.003), plasma PLTP activity ( p<0.001), triglycerides ( p= 0.01), C-reactive protein ( p<0.01) and insulin ( p<0.001) were higher, whereas HDL cholesterol was lower ( p<0.001) than in control subjects. Multiple stepwise linear regression analysis demonstrated that in type 2 diabetic patients IMT was independently associated with age ( p<0.001), sex ( p= 0.001), pulse pressure ( p= 0.003), plasma PLTP activity ( p= 0.03) and HDL cholesterol ( p= 0.03), but not with very low density lipoprotein+LDL cholesterol, triglycerides, C-reactive protein and insulin ( all p> 0.20). The relationship between plasma PLTP activity and IMT was not significant in control subjects. Conclusions/ interpretation: Plasma PLTP activity is a positive determinant of IMT in type 2 diabetes mellitus, suggesting that high PLTP activity is involved in accelerated atherosclerosis in this disease.