Objective To establish a mouse model of pneumonia induced by Acinetobacter baumannii, and to investigate the protective effect of sodium new houttuyfonate against Acinetobacter baumannii pulmonary infection. Methods Mice were divided into control group, pneumonia model group, and low- and high-dose sodium new houttuyfonate groups. C57BL/6 mice were pretreated with cyclophosphamide on days 4 and 1 before surgery, and since day 3 before treatment, the mice in the low- and high-dose sodium new houttuyfonate groups were given sodium new houttuyfonate. The Acinetobacter baumannii strain isolated in the clinical ICU was used to prepare fresh bacterial solution, and airway inoculation was performed to establish a mouse model of Acinetobacter baumannii pulmonary infection. Bacterial count in the lung and blood was determined at 24 and 72 hours after inoculation. Hematoxylin and eosin staining was used to observe inflammatory changes in lung tissue. The numbers of leukocytes and neutrophils and the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were measured. Results There was a significant increase in the number of bacteria in the lung and blood after the inoculation with Acinetobacter baumannii in mice (P<0.05), and the mice had serious inflammatory response and tissue injury, as well as significant increases in leukocyte count and levels of TNF-α and IL-1β in BALF (P<0.05). After the treatment with sodium new houttuyfonate, compared with the pneumonia model group, the low- and high-dose sodium new houttuyfonate groups had significantly lower numbers of bacteria in the lung and blood, significantly milder lung tissue injury, and significant increases in the numbers of leukocytes and neutrophils and the levels of TNF-α and IL-1β in BALF (P<0.05). Conclusion Sodium new houttuyfonate can significantly increase the number and activity of leukocytes in mice with Acinetobacter baumannii pulmonary infection and thus enhance anti-infection ability.