Tropical maize germplasm CML493 were artificial inocuting setosphaeria turcica in this study. The leaves surface present bit spot then gradually increase and enlargement along the extension of time. Methylation-sensitive amplification polymorphism (MSAP) technique and transcriptome sequencing (mRNA -seq) technique were used to analyze the DNA methylation pattern, DNA methylation level and mRNA expression of CML493. The results showed that the methylation sensitive amplification polymorphisms of each treatment group were 78.21% and 76.13%, and the methylation sensitive amplification polymorphisms of each treatment group were 21.79% and 23.87%. The total methylation rate increased by 5.49%, the total methylation rate increased by 14.24%, and the semi-methylation rate increased by 6.11%. When inoculated with bacteria solution after 6 days, the total methylation rate increased by 6.40%, the total methylation rate increased by 16.73%, and the semi-methylation rate increased by 5.57%. When inoculated with the bacteria solution on 12d, A total of 2298 coexpressed genes, 1434 coexpressed up-regulated genes and 769 coexpressed down-regulated genes were detected. The number of upregulated genes was significantly higher than that of down-regulated genes according to the volcanogram. A total of 5 gene IDs were screened out to be possibly involved in the regulation of inoculated Setosphaeria turcica. The total methylation and total methylation were closely related to the number of differentially expressed genes and down-regulated genes with the extension of the infection time.The number of hemimethylation was closely forecast related to the number of up-regulated genes .