Aim To investigate the diagnostic value of carotid ultrasonography combined with serum pentraxin 3 (PTX3) and lipoprotein-associated phospholipase A2 (Lp-PLA2) in atherosclerotic cerebral infarction. Methods 56 patients with acute ischemic stroke treated in neurology department of our hospital from January 2015 to December 2017 were randomly selected as observation group, and 50 healthy persons who underwent physical examination in our hospital during the same period were selected as control group. Carotid ultrasonography was performed in both groups, and venous blood was collected to detect PTX3 and Lp-PLA2 levels. The serum levels of PTX3 and Lp-PLA2 and the detection rates of carotid intima-media thickness (IMT) thickening, plaque and moderate to severe stenosis were compared between the two groups. The diagnostic value of carotid ultrasonography, PTX3, Lp-PLA2 alone and in combination for atherosclerotic cerebral infarction was analyzed. Results The serum levels of PTX3 and Lp-PLA2 in the observation group were significantly higher than those in the control group (P＜0.05), and the detection rates of carotid IMT thickening, plaque and moderate to severe stenosis were significantly higher than those in the control group (P＜0.05). The sensitivity and accuracy of carotid ultrasonography combined with PTX3 and Lp-PLA2 were 89.29% and 77.36%, which were significantly higher than those of PTX3 (73.21%, 71.69%), Lp-PLA2 (69.64%, 67.92%) and carotid ultrasonography (80.36%, 76.42%) with alone detecting (all P＜0.05). ROC curve showed that the area under curve (AUC) of carotid ultrasonography was 0.789, AUC of PTX3 was 0.764, AUC of Lp-PLA2 was 0.776, and AUC of combined detection was 0.909; The difference was statistically significant (P＜0.05). Conclusion Carotid ultrasonography combined with serum PTX3 and Lp-PLA2 detection can significantly improve the sensitivity and accuracy for diagnosis of atherosclerotic cerebral infarction.