Objective To explore the mechanism of LY294002 intervention on M2 macrophage polarization and airway inflammation in asthmatic mice.Methods The 24 male BALB/c mice were randomly divided into the blank control group,the asthma model group,the LY294002 group,and the dexamethasone group,with 6 mice in each group.The asthma mouse model was established by sensitization through intraperitoneal injection of ovalbumin and provocation via aerosol inhalation.After 7 days of continuous intraperitoneal drug administration,the airway inflammation and goblet cell hyperplasia in the lung tissues of mice were observed.Serum immunoglobulin E(IgE),interleukin-4(IL-4),and IL-25 were detected by ELISA,and inflammatory cell counts in bronchoalveolar lavage fluid were determined.Quantitative real-time polymerase chain reaction was used to detect the mRNA expressions of inflammatory factors IL-4,IL-13,and IL-25R,as well as M2 markers ARG-1 and Ym-1 in lung tissues.Western blotting was performed to detect the protein expressions of PI3K,p-PI3K,Akt,p-Akt,and M2 marker CD206 in lung tissues.Results Compared with the blank control group,the asthma model group had a higher total number of cells and greater percentages of eosinophils,neutrophils and lymphocytes(P<0.05),but a lower percentage of macrophages in bronchoalveolar lavage fluid(P<0.05).The total number of cells and the percentages of eosinophils,neutrophils and lymphocytes were lower(P<0.05),but the percentage of macrophage was higher in the LY294002 group and the dexamethasone group compared with the asthma model group(P<0.05).The serum levels of IgE,IL-4 and IL-25 in the asthma model group were higher than those in the blank control group(P<0.05),while they were lower in the LY294002 group and the dexamethasone group than in the asthma model group(P<0.05).The relative mRNA expressions of ARG-1,YM-1,IL-4,IL-13 and IL-25R in the asthma model group were higher than those in the blank control group(P<0.05),while they were lower in the LY294002 group and the dexamethasone group than in the asthma model group(P<0.05).The relative protein expressions of p-PI3K/PI3K,p-Akt/Akt and CD206 in the asthma model group were higher than those in the blank control group(P<0.05),while they were lower in the LY294002 group and the dexamethasone group than in the asthma model group(P<0.05).Conclusions LY294002 can significantly reduce the M2 polarization of lung tissues and alleviate airway inflammation in asthmatic mice,and its mechanism may be related to the PI3K/Akt signaling pathway.