Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies. Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group, and cyclophosphamide +fungal infection low, medium, and high dose groups, with 12 animals in each group. General clinical observations were performed daily, and the serum levels of immunoglobulin (Ig)G and IgM and galactomannan (GM) were detected by ELISA on the 3rd and 7th days of modeling. Simultaneously, the ratio of CD4⁺ and CD8⁺cells, content of white blood cells (WBCs) and neutrophils (Neu) in peripheral blood, the Aspergillus niger load in alveolar lavage, and morphological changes to rat lung tissue were observed. Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling, and rats in the cyclophosphamide + fungal infection group also had shortness of breath and audible wet rhonchi in the lungs. Compared with the normal control group, rats in the cyclophosphamide control group showed significant reductions in the levels of CD4⁺, WBC, Neu, IgG, and IgM in the blood, and their proportion of CD8⁺cells was significantly higher ( P<0. 05, P<0. 01 ). Compared with the cyclophosphamide control group, rats in the cyclophosphamide+fungal infection medium- and high-dose groups had significantly reduced blood levels of IgG, IgM, and CD4⁺ cells (P<0. 05, P<0. 01); while the cyclophosphamide+fungal infection low-, medium-, and high-dose groups had significantly reduced blood levels of WBC and Neu (P<0. 05, P<0. 01). Additionally, rats in the cyclophosphamide+fungal infection medium- and high-dose groups had significantly increased blood CD8⁺ cells (P<0. 05, P<0. 01), Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide + fungal infection low-, medium-, and high-dose groups compared with the cyclophosphamide control group (P<0. 05, P<0. 01). The lung tissues of the cyclophosphamide+fungal infection low-, medium-, and high-dose groups showed mycelial distribution and destruction of alveolar epithelium, increase of bronchial epithelial cup cells in the alveoli, and infiltration of inflammatory cells, and the degree of lesions was positively correlated with the modeling dose. Conclusions In this study, we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease. The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time, confirming that cellular immunity plays an important role in the pathogenesis of the disease. At the same time, Ig can also affect the development of invasive pulmonary aspergillosis, and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.