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OBJECTIVE To explore the protective effects and mechanism of ethanol extract of Inonotus obliquus (EEIO) injection on asthmatic mice. METHOD OVA was injected intraperitoneally and inhaled to produce the asthmatic model. Thirty two mice were randomly divided into four groups: control group, asthma group and I. obliquus groups of high and low dose. The concentrations of IL-4, IL-5, IL-13 and IFN-gamma in BALF, the phosphor-p38 MAPK in lung tissues were respectively measured by ELISA and Western blotting. The number of inflammatory cells in BALF and histopathology changes were observed. RESULT In asthmatic group, the number of inflammatory cells and the concentrations of IL-4, IL-5, IL-13 in BALF and phospho-p38 MAPK in lung tissue were higher, while IFN-gamma were lower than those in normal control mice (P < 0.05). In I. obliquus group, the number of inflammatory cells, the concentrations of IL-4, IL-5, IL-13 in BALF and phosphor-p38 MAPK in lung tissue were lower, but were higher than those in normal control mice (P < 0.05), and histropathology damage was alleviated significantly. There was no significant difference observed among the efficacies in the I. obliquus groups of high and low dose. CONCLUSION p38 MAPK may play a role in pathological process of asthma. I. obliquus effectively treats asthma by inhibiting the expression of phosphor-p38 MAPK, correcting the unbalance of IFN-gamma/IL-4 and decreasing the number of inflammatory cells.