Abstract Carotid atherosclerosis may be associated with neurosymptoms including cerebral infarction. IL-10 exerts atheroprotective effects, but its role in carotid disease is not fully defined. We aimed to investigate serum IL-10 levels in patients undergoing endarterectomy and their relation to the degree of carotid stenosis, plaque types and neurosymptoms. Two hundred consecutive patients with atherosclerotic carotid stenosis and 29 healthy controls were enrolled in this study. Plaque types were classified according to AHA criteria. Serum IL-10 levels were determined by ELISA. Patients undergoing endarterectomy had significantly higher circulating IL-10 levels (18.7 ± 3.2 pg/ml) in comparison with healthy controls (7.2 ± 1.8pg/ml; P =0.0001) and IL- 10 has good discriminatory efficacy between these two groups (ROC curve, AUC = 0.723, P=0.0001). Patients with < 70% and those with > 70% of carotid stenosis did not differ in terms of age, sex, cardiovascular risk factors except hypertension, neurosymptoms and AHA plaque types. Circulating IL-10 levels differed significantly among patients with different carotid plaque types (P = 0.002). Patients with uncomplicated plaques had significantly higher serum levels of IL-10 (23.0 ± 6.1 pg/ml) compared to those with complicated plaques (13.0 ±1.4 pg/ml, P=0.035) and IL-10 can differentiate patients between these two groups (ROC curve, AUC = 0.413, P= 0.035). Our findings reveal an important role for IL-10 in carotid atherosclerosis. IL-10 might be a potential biomarker in discriminating patients with carotid disease from healthy controls. Decreased serum levels of IL-10 are related to complicated carotid plaques.