Objective To investigate the correlation of the serum levels of a disintegrin and metalloproteinase with thrombospondin 1 （ADAMTS1） and endothelial cell-specific molecule-1 （ESM-1） with the nature and stenosis degree of carotid artery plaque in patients with ischemic stroke （IS）.Methods A retrospective analysis was performed for the clinical data of 124 IS patients who were admitted to The First Affiliated Hospital of Xinxiang Medical College from January 2019 to February 2023 （observation group）， and 124 healthy volunteers who underwent physical examination in the hospital were enrolled as control group. ELISA was used to measure the serum levels of ADAMTS1 and ESM-1. Spearman rank correlation analysis was used to investigate the correlation of the serum levels of ADAMTS1 and ESM-1 with the characteristics of carotid plaque. Multivariate logistic regression analysis was used to identify the influencing factors for the nature and stenosis degree of carotid plaque in IS patients. Receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the diagnostic performance of the serum levels of ADAMTS1 and ESM-1.Results The observation group had significantly higher serum levels of ADAMTS1 and ESM-1 than the control group （P<0.05）. Compared with the group without carotid artery plaques， the stable plaque group and the unstable plaque group had gradual increases in the serum levels of ADAMTS1 and ESM-1 （P<0.05）. The correlation analysis showed that the serum levels of ADAMTS1 and ESM-1 were positively correlated with carotid arteriosclerosis （P<0.05）. ADAMTS1 and ESM-1 were influencing factors for carotid artery lesions in IS patients （P<0.05）. The serum levels of ADAMTS1 and ESM-1 alone or in combination had an AUC of 0.759， 0.786， and 0.873， respectively， in diagnosing the nature of carotid plaque in IS patients， with a sensitivity of 65.45%， 80.00%， and 74.55%， respectively， and a specificity of 82.61%， 73.91%， and 93.48%， respectively， and the combination of the two indicators had a significantly better diagnostic performance than each indicator alone （P<0.05）. The serum levels of ADAMTS1 and ESM-1 alone or in combination had an AUC of 0.755， 0.804， and 0.873， respectively， in determining the degree of carotid stenosis in IS patients， with a sensitivity of 87.10%， 67.74%， and 80.64%， respectively， and a specificity of 60.78%， 84.31%， and 90.20%， respectively， and the combination of the two indicators had a significantly better diagnostic performance than each indicator alone （P<0.05）.Conclusions There are increases in the serum levels of ADAMTS1 and ESM-1 in IS patients， which are positively correlated with the nature and stenosis degree of carotid artery plaque， and the combination of these two indicators can be used as an auxiliary indicator for evaluating the nature and stenosis degree of carotid artery plaque in patients with IS.