BACKGROUND Diabetes mellitus (DM) is a major risk factor for cardiovascular events. The study purpose was to compare DM and non-DM (nDM) patients in terms of statin-induced change of plaque characteristics using intravascular ultrasound (IVUS) and coronary angioscopy. METHODS Patients with coronary artery disease and hypercholesterolemia who were enrolled to the TWINS were selected and classified into two groups: DM group and nDM group. Eleven DM patients and 28 nDM patients were studied. RESULTS Low-density lipoprotein cholesterol levels decreased significantly to a similar extent at weeks 28 and 80 from baseline in DM and nDM (p<0.001). The mean angioscopic color grades of yellow plaques in DM and nDM were similar at baseline and significantly decreased at week 80 from baseline in both groups, however, the mean change of angioscopic color grade from baseline in DM were not significantly decreased and the mean angioscopic color was significantly higher than that in nDM (1.34 vs. 1.00, p<0.05) at week 28. IVUS showed plaque volume reduction in both groups (p<0.01) except at week 80 in DM group, which was not statistically significant different compared to the baseline. CONCLUSION In DM patients, plaque volume regression by atorvastatin was shown to be attenuated, and its color improvement was significantly delayed. However, the yellowness became comparable between DM and nDM groups at week 80. These results indicate that patients with DM should be treated by intensive lipid-lowering therapy with atorvastatin for at least 80 weeks to stabilize vulnerable plaque.