Mastitis is one of the most common production diseases and economically the biggest and most important disease in the dairy industry. it causes a lot of economic loss to the dairy industry and the reduction of milk production is a small part of its effects. The immune response of the mammary gland to the presence of microorganisms causes mastitis (Li and Chen, 2019). The development of microarray technology provides the possibility of a comprehensive investigation of known genes in certain tissues such as the mammary gland in order to increase our knowledge of the defense mechanisms involved in the mammary gland, and identify gene networks and gene expression changes. (Lehours et al., 2011). The gene expression data was implemented with the accession number GSE50685. The criterion of Differential gene expression measurement was considered at the level of P-value < 05 and LogFC > 1 or LogFC<-1. STRING database and Cytoscape software were used to establish a gene network related to mastitis disease. In order to identify the genes with the greatest regulation effect, the genes with connected degrees above 7 were selected and studied. DAVID software was used to identify biological pathways. In this study, we found that FOXO1, ITGB1, HSP90AA1, HSP90AA1, IL2, IL6, and CXCL10 genes are the most linked genes. The enrichment results of the KEGG pathway indicated that highly connected genes were related to Mastitis. The first prominent gene is the FOXO1 gene, which plays a role in mammary gland immune and inflammatory regulation through the inhibition of EGFR-AKT signaling. The second gene is ITGB1 which researchers reported that TGF-β1 gene promoted the expression of Fn and ITGB1 genes on the surface of bovine mammary epithelial cells and contributed to mammary gland infection in vitro and in vivo. The results of this study imply that Fn and ITGB1 may be useful therapeutic targets for the treatment of mastitis in dairy cows. Another gene is HSP90AA1, which this gene promotes autophagy and inhibits apoptosis through PI3K/Akt/mTOR pathway and JNK/P38 pathway. IL2 gene is an anti-inflammatory cytokine that can inhibit natural killer cells. IL6 gene has also been reported to play a role in regulating mastitis inflammation by suppressing NF-kB signaling and CXCL10 genes have been introduced in previous studies as the "main gene" involved in the defense of mammary glands, and in another study has been proven, the relationship between the polymorphism of this gene and resistance to mastitis.