BACKGROUND: Atherosclerosis is accepted as an inflammatory disease. Evidence suggests that inflammation evoked by injury plays a pathogenic role in all stages of atherosclerosis. This study aimed to investigate whether the high-mobility group box-1 (HMGB1) a proinflammatory cytokine/nuclear protein, which is derived from both injured endothelium and activated macrophages/monocytes, could contribute to the progression of atherosclerosis and other cardiovascular diseases. METHODS: This study was designed as case–control. A total of 135 patients who referred to the hospital due to angina pectoris had the diagnosis of unstable angina and were candidates of angiography were recruited in this study. Forty patients who had coronary artery disease confirmed by angiography were considered as case group and control group consists of 40 persons who had no plaque, and 55 persons were excluded according to the exclusion criteria. At first, a questionnaire was filled for each patient including demographic factors and their medical history. Then a blood sample was taken to assess the level of HMGB1. Data were analyzed using SPSS, Student’s independent t-test, and chi-square tests. RESULTS: The mean plasma level of HMGB1 in the case group was 27.1 ± 2.9 ng/ml, while it was 19.6 ± 1.9 ng/ml in control groups (P = 0.03). The odds ratio for coronary artery plaque associated with high (> 15.03 ng/ml) levels of HMGB1 was 2.50 (95% confidence interval, 1.02-6.17, P = 0.03). CONCLUSION: Increased plasma HMGB1 concentration may be associated with an increased risk of coronary atherosclerosis.   Keywords: High-Mobility Group Box-1, Coronary Artery Diseases, Inflammation, Biomarkers