Introduction: Bronchial asthma is a multifaceted respiratory disorder that represents a significant global public health concern, afflicting millions of individuals and resulting in considerable morbidity and mortality. Aim of Work: to unravel the intricate ultra-structural and cyto-molecular potential impacts of exosomes released by mesenchymal stem cells (MSCs) as biocompatible nanocarriers of miR-146 on experimentally induced bronchial asthma. Materials and Methods: Thirty-two male adult albino rats were splitted into three groups. Group I (control group), group II (experimentally induced asthma group): Every rat got 25 µg house dust mite (HDM) extract suspended in 35 µL of saline for five sequential days weekly for four weeks intranasally, and group III (exosome-treated groups): rats were administered HDM as group II, and after two weeks, they received 100 µg MSC-derived exosomes in 0.5 ml PBS intravenous through the tail vein, once/day for two weeks. Pulmonary tissue samples were examined for histopathological, ultrastructural, and NF-κB immune expression beside RT-PCR estimation of miR-146a, IRAK1, and NF-κB. Results: observable morphological and ultrastructural restoration of pulmonary tissue architecture in the MSCs exosomes-treated group compared to induced asthma group were recorded. Furthermore, the significant suppression of IRAK1 and NF-κB, along with the expantion of miR-146a and reduced immunohistochemical representation of NF-κB in the exosomes-treated group, indicated the potential molecular mechanisms for the observed histo-morphometric impacts. Conclusion: our study outlined the therapeutic implicit of miRNA-146 in mesenchymal stem cell exosomes via IRAK1/NF-κB pathway as a novel and effective approach for managing bronchial asthma and paving the way for further research