Objective To investigate the relationship between microbial colonization of the lower respiratory tract and inflammatory indexes of lung infection in patients with chronic obstructive pulmonary disease (COPD). Methods 189 patients with COPD in the Department of Laboratory of Pingdingshan Hewu General Hospital from May 2021 to April 2023 were selected as research objects. According to the occurrence of lung infection, they divided into infected group and non-infected group. According to the presence or absence of respiratory microbial colonization group, they were divided into colonization group and non-colonization group, and the serum indexes of procalcitonin (PCT), hypersensitivity C-reactive protein (hs-CRP), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) levels were compared between each group, and the correlation between lower respiratory tract microbial colonization and inflammatory markers of lung infection in patients with COPD was analyzed by Spearman. Results Among the 189 patients, the infected accounted for 62.96% (119/189) and 233 strains of pathogenic bacteria were detected, including 72.53% (169/233) of gram-negative bacteria, 17.59% (41/233) of gram-positive bacteria and 9.87% (23/233) of fungi. Microbial colonization of the lower respiratory tract accounted for 29.10% (55/189). The incidence of lower respiratory tract colonization, PCT, hs-CRP, IL-8 and TNF-α levels in the infected group were higher than those in the non-infected group (P<0.05). The levels of PCT, HS-CRP, IL-8 and TNF-α in the colonized group were higher than those in the non-colonized group (P<0.05). Pulmonary infection in COPD patients was positively correlated with lower respiratory tract microbial colonization, PCT, HS-CRP, IL-8 and TNF-α (P<0.05). Conclusion The microbial colonization strains of the lower respiratory tract of COPD patients are mainly gram-negative bacteria and are closely related to lung infection, which may increase the incidence of lung infection by aggravating the inflammatory response