Objective: To explore the value of contrast-enhanced ultrasound (CEUS) combined with serum markers for the identification of unstable plaques and mixed plaques. Methods:190 patients with carotid atherosclerotic plaques were selected from February 2018 to August 2020 in our hospital who underwent routine ultrasound examination. All patients underwent contrast-enhanced ultrasound, serum Lp-PLA2, and hs-CRP detection before surgery. Taking pathological results as the gold standard, it was divided into unstable plaques (138 cases) and stable plaques (52 cases) according to the stability of plaques; according to the nature of plaques, it was divided into soft plaque group (138 cases) and hard plaque group (20 cases) and mixed plaque group (32 cases). Compare the differences of contrast-enhanced ultrasound, serum Lp-PLA2, hs-CRP levels among the groups. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value index expression of contrast-enhanced ultrasound, serum markers alone or in combination in the diagnosis of unstable plaques are different in diagnostic efficiency.Results: The difference of CUES diagnosis of plaque stability was statistically significant (x_²=93.479, P=0.000). Different types of carotid atherosclerotic plaques have different CUES enhancement grades. When the echo of the plaque is lower, its enhancement is more obvious, and the grade is higher, and the distribution difference has statistical significance (x_²=21.837, P=0.000). Serum hs-CRP[(23.17±0.53)mg/L] and Lp-PLA2[(57.36±4.22)ug/L] in the unstable plaque group were significantly higher than those in the stable plaque group [(16.32±0.56)mg/L ], [(46.73±4.14)ug/L], and the difference was statistically significant (t=0.347, 8.432, P=0.000, 0.000). The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of CUES combined with serum markers in the diagnosis of unstable plaque were the highest, and the difference was statistically significant (P<0.05). Conclusion: Contrast-enhanced ultrasound combined with serum hs-CRP and Lp-PLA2 levels have a certain value in the differential diagnosis of unstable plaques and mixed plaques, which can help to identify unstable plaques and mixed plaques early and further guide the choice of clinical treatment options.