Abstract: In this study, gpt transgenic mouse model was used to evaluate the genotoxicity of e-cigarette aerosol. Taking peripheral blood reticulocytes as experimental assay, the effects of e-cigarette aerosol on chromosome damage were detected by micronucleus test, and the mutagenic effect of e-cigarette aerosol was detected by Pig-a gene mutation test. Using lung tissue as experimental assay, the effects of e-cigarette aerosol on the gene expression of mmu-miR-34a, mmu-let-7a, Akt1, Il-6 and Tnf-a were detected by real-time fluorescent quantitative PCR. The results showed that comparing with the control group, micronucleus frequency, Pig-a mutation frequency and RET% were not significantly different in the low-and high-dose e-cigarette aerosol group and the low-and high-dose group of 3R4F reference cigarette smoke (P>0.05). The mmu-miR-34a, Il-6 and Tnf-a in the low-and high-dose groups of e-cigarette aerosol significantly decreased (P < 0.05), and the expression of mmu-let-7a increased (P < 0.05) in the high-dose group. The mmu-miR-34a, mmu-let-7a and Tnf-a in the high-dose group of 3R4F reference cigarette smoke significantly reduced (P < 0.05).In conclusion, the genotoxicity of e-cigarette aerosol could not be detected in gpt delta transgenic mice model, however e-cigarette aerosol significantly affected the mRNA expression of DNA damage and inflammation-related genes.