There is limited evidence on the association between insulin resistance (IR) and carotid plaque was reported in prospective study. We aimed to exploit the relationship between IR and carotid plaque in a prospective cohort study.The study was performed in a functional community cohort in urban Beijing. In 2015, a total of 7061 individuals without intima-media thickness (IMT) thickening and carotid artery plaque were recruited and followed up until 2019. Restricted cubic spline was conducted to exploit the dose-response relationship between carotid plaque and baseline HOMA-IR or TyG index as continuous variables. Logistic regression was used to analyze the associations between carotid plaque and HOMA-IR or TyG index. During the average 4 years follow-up, 589 subjects developed carotid plaque. Both HOMA-IR and TyG index showed significant linear dose-response relationship on carotid plaque (p < 0.001). The RRs (95%CI) for subjects with baseline HOMA-IR in quartile 2, quartile 3 and quartile 4 were 1.52 (1.14-2.04), 1.86 (1.40-2.46), and 2.55 (1.94-3.35) compared to quartile 1, respectively. Compared to the first quartile of TyG, the RRs (95%CI) for subjects in quartile 2, quartile 3 and quartile 4 were 1.43 (1.08-1.90), 1.59 (1.20-2.12), and 1.69 (1.26-2.25), respectively. In total population, the predictive ability of HOMA-IR for carotid plaque was significantly better than that of TyG index (p = 0.025).IR is an independent risk factor of carotid plaque. Both HOMA-IR and TyG has significant predictive ability for carotid plaque.Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.