Objective The aim of this study was to investigate the effects and mechanisms of bone marrow mesenchymal stem cell exosomes on the mouse asthma models. Methods C57/6J mice were divided into control group， model group， exosome （5， 10， and 20 μg）， and exosome （20 μg） + RS09 TFA group. After administration of the respective treatment， airway resistance was measured in each group of mice. Hematoxylin and eosin （HE） staining was used to detect airway damage in mice. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the concentrations of inflammatory factors interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） in the alveolar fluid of mice. The colorimetric method was used to determine the concentrations of malondialdehyde （MDA）， catalase （CAT）， and superoxide dismutase （SOD） in the alveolar fluid. Western blot was used to detect the expression of Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor κB （NF-κB） in the lung tissues of mice. Results Compared with the model group， the airway resistance in the exosome 5， 10， 20 μg groups decreased significantly （P < 0.05）； the concentrations of IL-4， IL-5， IL-13， and MDA in the alveolar fluid of mice decreased significantly （P < 0.05）； while the concentrations of CAT and SOD increased significantly （P < 0.05）； additionally， the expression of TLR4， MyD88， and NF-κB were all significantly downregulated （P < 0.05）. Compared with the exosome 20 μg group， the airway resistance in the exosome 20 μg + RS09 TFA group increased significantly （P < 0.05）， the concentrations of IL-4， IL-5， IL-13， and MDA in the alveolar fluid of mice increased significantly （P < 0.05）， while the concentrations of CAT and SOD decreased significantly （P < 0.05）， the expression of TLR4， MyD88， and NF-κB were all significantly upregulated （P < 0.05）. Conclusion Bone marrow mesenchymal stem cell exosomes can alleviate mouse asthma by inhibiting the TLR4/MyD88/NF-κB signaling pathway.