OBJECTIVE: To analyze the difference in gene expression profiles and screen silicosis development related differentially expressed genes(DEGs) and signaling pathways in peripheral blood specimens of rats exposed to silica dust using bioinformatics and gene chip. METHODS: GSE27023 gene expression profiles of peripheral blood samples of rats exposed to silica dust were downloaded from Gene Expression Omnibus database. After screening of the DEGs through paired-sample t-test and fold change method,DEGs related to rats exposed to silica dust was performed by Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The protein-protein interaction(PPI) network was constructed with the Search Tool for the Retrieval of Interacting Genes database and visualized using the software Cytoscape. RESULTS: Of the 2 767 DEGs screened,1 363 were up-regulated and1 404 were down-regulated. KEGG pathway enrichment analysis showed that 39 signaling pathways,such as the calcium signaling pathway,neuroactive ligand-receptor interaction,Ras-related protein 1 signaling pathway,were significantly enriched. DEGs enrichment and significance reached the highest level in the calcium signaling pathway. PPI network and module analysis suggested that mitogen-activated protein kinase 14(Mapk14),DNA-directed RNA PolymeraseⅡ,V-erb-a erythroblastic leukemia viral oncogene homolog 4,B-cell lymphoma-2(Bcl-2),receptor interacting serine/threonine kinase 4,PH domain leucine-rich repeat protein phosphatase 2,DNA-directed RNA polymerase Ⅲ,neurogenic locus notch homolog protein 1,histone deacetylase 1,yeast switch in mating type/Sucrose non fermentation related,matrix associated,actin dependent regulator of chromatin,subfamily a,member 4 were top 10 hub-proteins. Mapk14 had the highest node degree in up-regulated DEGs,and Bcl-2 had the highest node degree in down-regulated DEGs. CONCLUSION: We found 39 signaling pathways and 10 DEGs that are related to toxicity caused by exposure to silica dust in rats by analysis of peripheral blood gene chip data. Among them,calcium signaling pathway,Mapk14 and Bcl-2 may play important roles in the development and progress of silicosis in rats.