Objective We detected the expression of macrophage-derived cytokines in macrophage of Cryptococcus neoformans infection mouse model to explore the role of those cytokines in pathogenesis of infection mouse.Methods A mouse model of Cryptococcus neoformans infection was established by inhalation of Cryptococcus neoformans through one nostril. On day 1, 4, 7, 11, 14, 18, 21 after inoculation, the infected lung were observed by histopathological analysis. Macrophage-derived cytokines (IL-6、IL-8、TGF-β、TNF-α)were detected by RT-PCR.Results Histopathological examination showed few Cryptococcus neoformans distributed in lung on 4 days and granuloma formation on 7 days after infection. There were significant inflammatory cellular infiltration in the lung tissue on 11 days and a large number of Cryptococcus neoformans in granuloma on 14 days after infection. At 18 and 21 days,diffuse distribution of Cryptococcus neoformans in the lung and the lung necrosis were observed. The mRNA expression of TGF-βand IL-6 reached to the peak at 14 days, then decreased gradually.Conclusion TGF-βwas involved in regulating the anti-fungal immunity in Cryptococcus neoformans infection mouse.