The aim of this study was to explore the effect of inflammation-mediated by NF-κB on lung injury of mice with invasive pulmonary aspergillosis. The mice were divided into three groups including the group of normal mice, the group of normal mice with infection and the group of IPA mice. The mice were sacrificed on day 4 post-infection. The lung tissues from each group were collected for observing the pathological alteration, evaluating histological scores of NF-κB p65 with immuno-histochemistry stain, detecting mRNA expression level of TNF-α and IFN-γ in comparison to β-tublin in ratio of densitometric units using RT-PCR and measuring MPO of neutrophils with colorimetry. The pathological analysis showed the normal structure and no inflammatory reaction in the lungs of the normal mice; and the infiltration of inflammatory cells, weak injury and no germination of spore into hypha in the lungs of normal mice infected with A. fumigatus and serious injury like destruction of alveolar structure, bleeding and germination of spore into hypha in the lungs of IPA mice. The expression level of TNF-a and IFN-γ, histological score of NF-κB p65 and activity of MPO in both groups of normal mice infected with A. fumigatus and IPA were higher than in the normal mice group(P<0.05). But histological score of NF-κB p65 and activity of MPO in IPA mice were higher than in normal mice infected with A. fumigatus(P<0.05). The results suggested that the expression of TNF-a and IFN-g as well as recruitment of neutrophils that were promoted by the signal pathway mediated by NF-κB activated by infection of A. fumigatus may be one of the factors that cause the seriously pathological injury of lungs in the mice with invasive pulmonary aspergillosis.