Aim: To study the effect of long-term glucose feeding on aortic lipid composition by using the time of flight-secondary ion mass spectrometry ( TOF-SIMS). Method: Rats were divided into two groups, drinking water with or without 10% glucose from birth to 6 months of age. The aortic wall was dissected out, high-pressure frozen, freeze-fractured, freeze-dried and analyzed by TOF-SIMS using a Bismuth cluster ion source. Surface spectra were taken from standardized regions of the vessel wall. Results: Different peaks, such as cholesterol, fatty acids ( FAs) and diacylglycerols ( DAGs), were identified by the principal component analysis as carries of variance between two groups. These peaks were then compared by conventional t-test. Our data showed that the intensity of cholesterol, but not FAs and DAGs, was significantly decreased in the glucose-drinking rat. Moreover, the long-term glucose intake changed ratios between different FAs in the aorta. Conclusion: The long-term glucose intake led to decreased cholesterol intensity in the aortic wall and this effect was revealed through a global analytical approach with objective selection of significant variables. (C) 2008 Elsevier B. V. All rights reserved.