Objective To evaluate the clinical value of the serum level of high mobility group box-1 protein(HMGB1) in coronary heart disease(CHD) patients accompanied with type 2 diabetes mellitus(T2DM). Methods A cohort of 60 CHD patients diagnosed by coronary angiography, with age ranging from 43 to 80(66±8)years, who were admitted to our department from March to November 2009 were subjected in this study. They were divided into 2 groups according to whether they were complicated with DM or not, 30 cases with DM in group A and 30 cases without DM in group B. Their fasting venous blood samples were collected for the serum levels of HMGB1, high sensitivity C-reactive protein(hs-CRP), fasting blood glucose (FBG), glycosylated hemoglobin A1c(HbA1c), and blood lipids. Gensini score was used to assess the severity of coronary artery lesion. All the parameters were compared and analyzed between 2 groups. Results The serum levels of HMGB1, hs-CRP, FBG and HbA1c were significantly higher in those with DM than those without(all P＜0.05). The patients accompanied with DM also had significantly higher Gensini score and percentage of triple vessel lesion than those without DM(both P＜0.05). Simple correlation analysis indicated that the severity of the coronary artery lesion was significantly correlated with the serum levels of HMGB1, hs-CRP, triglycerides(TG), total cholesterol (TC), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), and body mass index(P＜0.01). Conclusion CHD accompanied with DM aggravates the severity of coronary artery lesions. Elevated serum level of HMGB1 is not only an important risk factor for diabetic patients with CHD, but also an important indicator to reflect the diffuse and severe lesions of coronary artery in CHD patients with DM.