Abstract: OBJECTIVE To explore the influence of Aspergillus infection on macrophage function of the patients with rheumatoid arthritis and analyze the regulatory mechanisms. METHODS A total of 81 patients with rheumatoid arthritis who were treated in Tianjin Fifth Central Hospital from Sep 2020 to Aug 2022 were recruited as the research subjects and were divided into the infection group with 33 cases and the no infection group with 48 cases according to the status of pulmonary Aspergillus infection, meanwhile, 50 healthy people who received physical examination were chosen as the healthy group. The percentage of macrophages in sputum specimens or respiratory tract secretions, phagocytic function and levels of related receptors hypoxia-inducible factor -1α(HIF-1α), Bcl-2 homeodomain protein antibody (Beclin-1), microtubule-associated protein light chain 3I(LC3-I), microtubule-associated protein light chain 3II(LC3-II)mRNA and protein activation were detected for the research subjects. RESULTS The total counts of cells of the infection group were higher than those of the no infection group and the healthy group(P＜0.05). The percentage of macrophage of the infection group was lower than that of the no infection group and the healthy group. The phagocytic function, from high to low, were in order as follows: the healthy group, the infection group, the no infection group(P＜0.05). The relative expression levels of HIF-1αmRNA and protein of the infection group were higher than those of the no infection group and the healthy group, while the relative expression levels of Beclin-1, LC3-I, LC3-II mRNA and proteins of the infection group were lower than those of the no infection group(P＜0.05). CONCLUSION Aspergillus intervenes in the phagocytic function of macrophage of the rheumatoid arthritis patients and promotes the phagocytic function of macrophage by activating hypoxia-inducible factor 1α, indicating that it may be a self-defense mechanism against the invasion of pathogens.