Aim The differential gene expression, signaling pathways and protein network were analyzed from the gene chip data for carotid atherosclerotic plaques. Methods GSE43292 was downloaded from the gene expression omnibus (GEO) database and the data was adjusted. The significant differential genes were analyzed by R software in GSE43292. The geneontolgy (GO) analysis and pathway analysis were performed by bioinformatics GSEA, and the significant differential gene was analyzed by Cytoscape. Results After GSE42392 was analyzed, the 87 up-regulated genes and the 60 down-regulated genes were found as the significant different expression gene (P<0.01) between the atherosclerotic plaques and the distant tissues in carotid artery. The heatmap showed the different expression genes. The enriched GO analysis of GSEA revealed that the main differential expressions were associated with the antigen binding, the serine hydrolase activity and the chemokine receptor binding. The pathway analysis of GSEA revealed that the main differential expression were associated with hematopoietic stem cells, lysosomal and cytokine receptor interactions. Cytoscape analysis performed the five core genes, including IL-8, CXCL-10, SELE, MMP-9 and IL-18. Conclusions The bioinformatics analysis of GSE42392 data revealed that the differential genes enriched the related signaling pathways and the core genes were found between the atherosclerotic plaque and the distant tissue in carotid atherosclerotic plaques. These research provided the basic data for atherosclerosis research and treatment.