Abstract: OBJECTIVE To explore the influence of COP9 signalosome (CSN) complex gene deletion on addicted to infringe central nervous system of Cryptococcus neoformans and analyze the possible mechanisms so as to provide experimental data for research on the targets of antifungal drugs. METHODS The cyclophosphamide immunosuppressive C57BL/6 mice were treated with tail intravenous injection of H99 strains, COP9 signalosome CSN1201 gene deletion strains, and normal saline so as to build the mice intravenous injection infection models: the H99 group, the CSN1201 △ group, and the control group, with 10 mice in each.All of the data were statistically analyzed by using SPSS 15.0 software. RESULTS The colony growth of the H99 group was found after the fungal culture of mice brain tissues was performed for 12 hours, with the growth rate rapid, and C.neoformans strains were displayed by PAS staining.The culture of brain tissues was negative in the CSN1201△ group and the control group, and C.neoformans strains were not displayed by PAS staining.The level of expression of RhoA protein in the mice brain tissues of the H99 group was increased with the time, as compared with the control group, it was increased significantly after the culture for 24-72 hours.The level of expression of Rac1 or Cdc42 protein did not change with the time, however, as compared with the control group, they were increased significantly (P＜0.05). CONCLUSION The COP9 signalosome CSN1201 gene deletion may reduce the C.neoformans ability to pass through the blood-brain barrier, and the effect pathway may be associated with the regulation of brain microvascular endothelial cells tight junction protein cytoskeleton rearrangement.