Abstract: In order to explore the virus clearance mechanism of the lapinized attenuated strain of Classical swine fever virus（Chinese strain, C strain） in rabbits, New Zealand rabbits were used in this experiment as materials. After 7 days of adaptive feeding, they were randomly divided into 3 groups for C strain inoculation, namely one control group and two test groups, 6 rabbits in each group. The rabbits were sacrificed by air injection into the ear vein on the 5 th and 9 th days after C strain infection, and then the spleen was taken out, named T1 and T2 samples; and the total RNA of the spleen was extracted by TRIzol method, and the sequencing and analysis of the transcriptome of rabbit spleen were carried out by mRNA-Seq technology. Using control rabbit genome as a reference, differentially expressed genes were screened out; and GO functional enrichment analysis and KEGG signal pathway analysis were performed, and real-time fluorescent quantitative PCR method was used to verify some differential genes. The results showed that compared with the control group, the T1 samples obtained 61 up-regulated genes and 25 down-regulated genes after the infection with the C strain, respectively, and the T2 samples had 22 and 8 respectively. Differential genes in T1 samples were mapped to 109 entries, and differential genes in T2 samples were mapped to 61 entries; differential genes in T1 and T2 samples were both enriched in metabolic processes and cellular processes. Differential genes in T1 samples mainly involved chemokine signaling pathways, cytokine and their receptor pathways, cell cycle pathways, RIG-I-like signaling pathways, and Toll like receptor signaling pathways. Differential genes in T2 samples mainly involved arginine and proline Metabolic pathway, vitamin B₆ metabolic pathway and renin-angiotensin system pathway. The real-time fluorescent quantitative PCR verification results were basically consistent with the analysis results of mRNA-Seq technology. The results suggested that after rabbits were infected with the C strain, T1 samples mainly resisted and cleared the virus through immune response, and T2 samples mainly restored the normal function of body cells through the regulation of cell metabolism-related genes.