Objective: To explore the effect of lipopolysaccharide intervention program on Legionella pneumonia. Methods: C3H/HeN mice (6-8 weeks old) were used as experimental animals. The mice were randomly divided into lipopolysaccharide intervention, non-lipopolysaccharide intervention and control groups. Each group was again divided into three time points: 12 h, 24 h and 48 h. Mice in the lipopolysaccharide intervention group were intraperitoneally injected with E. coli lipopolysaccharide (100 ng per mice), and the rest groups were intraperitoneally injected with normal saline. After 24 hours, mice in the lipopolysaccharide intervention and the non-intervention groups mice were infected with Legionella by tracheal injection and the control group was given the same amount of saline. All the mice were killed at 12, 24 and 48 hours respectively. The mice were anatomized, lungs of the mice were separated and weighed. Organ coefficients (lung weight/body weight of mice) were calculated. 1 ml Orbital blood was collected. Toll-like receptor 4 (TLR4) levels of peripheral blood mononuclear cells were measured by flow cytometry. The contents of TNF-α and IL-1β in the upper left lung lobe were measured by ELISA. Results: In the lung organs, the coefficients of lipopolysaccharide non-intervention group were higher than the other groups and there was no significant difference seen between the lipopolysaccharide intervention group and the controls. TLR4 peaked at 12 hours in both the lipopolysaccharide intervention and the non-intervention groups while the TLR4 level in the intervention group was higher than that in the non-intervention group. There were no significant differences appeared on the TLR4 expression levels between the two Legionella pneumonia modelled groups at 24 or 48 hours. There was no significant difference seen regarding the concentration of TNF-α and IL-1β between the intervention and the control groups. The secretion levels of TNF-α and IL-1β in the non-intervention group were higher than those in the intervention group at each time point. Conclusion The lipopolysaccharide intervention program may alleviate the inflammatory symptoms of Legionella infection.