Background: Bilirubin prevents oxidative modification of low density lipoprotein, and may protect vessels from atherosclerosis. Several studies showed an inverse relationship between serum bilirubin and coronary artery disease. However, there are some needs to clarify the relationship between serum bilirubin and carotid atherosclerosis in type 2 diabetes, especially. Methods: A total of 346 type 2 diabetic patients, between 35 and 95 years of age (146 men and 200 women), were studied. Subjects with normal serum total bilirubin were divided into two groups, according to their serum total bilirubin levels (group I, total bilirubin ≥ 1.0 mg/dL [n = 59]; group II, total bilirubin ≤ 0.5 mg/dL [n = 76]). Carotid intima-media thickness (IMT) and plaque scores were measured by ultrasonography. Carotid atherosclerosis was defined by the presence of plaque or more than 1 mm of common carotid IMT. Results: Carotid IMT was positively correlated with age, duration of diabetes and hypertension, high sensitive C-reactive protein (hs-CRP) and fibrinogen, but, it was negatively correlated with bilirubin, gamma glutaryltransferase, albumin, hemoglobin, cystatin C and estimated-glomerular filtration rate (GFR) in all subjects. After controlling for sex, age and levels of hemoglobin, direct bilirubin only was negatively correlated with carotid IMT (r = -0.151, P = 0.034). Low serum total bilirubin group had a lot of female, long duration of diabetes and hypertension, higher hs-CRP, platelet counts, serum creatinine, HbA1c and homeostasis model assessmentinsulin resistance, lower albumin, hemoglobin, estimated-GFR and quantitative insulin sensitivity check index. Carotid IMT and plaque scores were significantly greater in low serum bilirubin group (0.785 ± 0.210 mm vs. 0.678 ± 0.146 mm, P < 0.01; 1.95 ± 2.56 vs. 1.03 ± 1.40, P < 0.05, respectively) than in the high serum bilirubin group. Multivariate logistic regression analysis showed that age, serum albumin and total bilirubin were independent associated factors for carotid atherosclerosis in type 2 diabetic women. Conclusion: Total bilirubin is inversely correlated with carotid atherosclerosis in type 2 diabetic patients, and it is an independent associated factor for carotid atherosclerosis in women. (Endocrinol Metab 27:126-131, 2012)