Abstract: OBJECTIVE To investigate the influencing factors of pulmonary infection in patients with type 2 diabetes mellitus (T2DM), and surface-active protein D (SP-D) gene polymorphism and Smad proteins detection. METHODS A total of 103 patients with T2DM complicated with pulmonary infection who were diagnosed and treated in People's Hospital of East-West Lake District, Wuhan between Aug. 2018 and Jun. 2021 were selected, and divided into infected group (20 cases) and uninfected group (83 cases) according to the presence or absence of pulmonary infection. The pathogenic bacteria of infected patients were analyzed, and the SP-D gene polymorphism and expression of Smad protein were detected in all patients. Logistic regression analysis was used to analyze the influencing factors of pulmonary infection in patients with T2DM. RESULTS A total of 59 strains of pathogenic bacteria were isolated from patients with lung infection, of which 37 strains of Gram-negative bacteria accounted for 62.71%, 18 strains of Gram-positive bacteria accounted for 30.51%, and 4 strains of fungi accounted for 6.78%. The CC gene frequency of SP-D gene rs721917 in the infected group was higher than that in the uninfected group, and CT gene frequency was lower than that in the uninfected group (P<0.05). There was statistically significant differences in allele frequencies between the two groups (P<0.05). The expression of serum Smad 1, Smad 2 and Smad 3 in the infected group were higher than those in the uninfected group (P<0.05). Logistic regression analysis showed that glycosylated hemoglobin and CC gene frequency of SP-D gene rs721917 were the influencing factors of pulmonary infection in patients with T2DM (P<0.05). CONCLUSION Gram-negative bacteria was main pathogenic bacteria of pulmonary infection in patients with T2DM. The occurrence of pulmonary infection was related to glycosylated hemoglobin and CC gene frequency of SP-D gene rs721917.