The aim of this study was to compare the effects of two different doses of ambroxol (AMB) co-administered with azithromycin (AZIT) on the concentrations of bronchoalveolar lavage fluid (BALF) cytokines and serum biochemical parameters in an lipopolysaccharide (LPS)-induced acute lung injury mouse model. A total of 78 male Swiss albino mice were used for this investigation. After six mice had been separated as the control group (0 hours), the remaining animals were divided into the following three equal groups: LPS, LPS+AZIT+AMB30 and LPS+AZIT+AMB70. LPS, AZIT and AMB were administered intraperitoneally. BALF and serum samples were collected before (0 hour) and after applications at 4, 8, 16 and 24 hours under general anaesthesia, and then all mice were euthanised by cervical dislocation. Concentrations of tumor necrosis factor (TNF)α, interleukin (IL)-6 and IL-10 in BALF and aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine concentrations in serum were determined. Elevated TNFα and IL-6 concentrations in the LPS group were prevented at 8 and 16 hours in LPS+AZIT+AMB30 group. In addition, both treatment groups inhibited elevated IL-6 concentrations in the LPS group at 16 hours. LPS+AZIT+AMB30 and LPS+AZIT+AMB70 increased IL-10 concentrations at 16 and 4 hours, respectively. LPS caused significant elevations in urea concentrations at all sampling times and statistical fluctuations in other parameters at different sampling times. The increased ALP concentration in LPS group decreased in the treatment groups at 8 hours. In conclusion, the combination of low-dose AMB and AZIT may achieve beneficial effects in pulmonary infections by influencing the cytokine network.