Mastitis or inflammation of the mammary glands in dairy cattle has significant implications for the health and welfare of livestock and leads to abundance economic losses to the dairy industry. The aims of current study were to compare the gene expression profile of the mammary gland epithelial cell arrays contaminated with E. coli pathogens, as well as identification of the basic biological mechanisms involved in the mastitis by E.coli and introduction of key regulatory genes via the genetic adjustment network. In this study, gene expression microarray datasets extracted from a database of GEO No. GSE24560 access was used. This data refers to the cells extracted from mammary gland epithelial cells in two groups of cattle selected for high and low suceptiblity to mastitis affected by a specific QTL, located on chromosome number 18. These cells were contaminated by E. coli pathogens and the gene expression profile for each treatment and each SCS-BTA18-QTL alleles at three different hours of 1, 6 and 24 were measured. The quality control and normalization of data were carried out in the R environment software, with affy and arrayQualityMetrix packages respectively. Differentially express genes were analyzed by using Limma package. Two different analysis were performed to compare alleles. In the first analysis, the interaction between the control group and the treatment group (contaminated) was investigated at three times (1, 6 and 24 hours) for each genotype, and in the second analysis, the interaction of two genotypes was directly investigated at the time mentioned before. The results of differentially express genes showed that the largest number of significant genes (adj.P.Val = 0.05 and logFC 0.05) was for both genotypes at 24 hours after contamintation with E.coli , So that in the first analysis, for the favorable (Q) and unfavorable (q) genotypes, 295 genes (233 genes Up-regulate and 62 genes Down-regulated) and 74 genes (63 genes Up-regulate and 11 genes Down-regulate) were differentially expressed, respectively. However, in the second analysis, 569 genes (312 genes Up-regulate and 257 genes Down-regulate) showed differentially expressed. The results showed that the favorable genotype helps to correct the suppression of metabolic processes during infection and also to regulate signaling pathways related to immune response and inflammation. Functional enrichment analysis of the genes and the gene regulatory network were performed for the second analysis gene list. Many of the pathways suppressed by genes differentially expressed genes are related to trigger the inflammatory and immune responses, including leukocyte activation, response to endogenous stimulus, positive regulation of signaling that causes moderate responses to the infection, as well as pathways associated with growth, cell proliferation, and reproductive process enriched by down-regulated genes. Results of gene regulatory network showed that TP53 and SP1 transcription factors, ligands including INS, IL1B, IFNG, TGFB1, EGF and protein kinase MAPK1 are common altered factors in constructed networks. Key Words Dairy cattle, mastitis, E.coli , Transcriptome, Differentially Expressed Genes, Gene Regulatory Network