〔Abstract〕 Objective To investigate the role and related molecular mechanisms of vitamin D3(VitD3) in airway inflammation and oxidative stress response in bronchial asthma mice. Methods Twenty-eight female C57BL/6 mice were randomly divided into a control group(Ctrl) and a model group. The model group mice were sensitized using ovalbumin(OVA) to establish an asthma model, and were further divided into an asthma(Asthma) group, VitD3treatment(Asthma+VitD3) group, and Forkhead Box O1(FOXO1) inhibitor AS1842856 treatment(Asthma+AS) group. Lung resistance(LR) changes were measured in each group of mice. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, and IL-18 in bronchoalveolar lavage fluid(BALF). Western blot was used to determine the expression levels of FOXO1, NOD-like receptor pyrin domain containing 3(NLRP3), Caspase-1, and apoptosis-associated speck-like protein(ASC) in lung tissue. Results Compared to the Ctrl group mice, LR increased in the Asthma group mice(P<0.01). Compared to the Asthma group, LR decreased in the Asthma+VitD3and Asthma+AS group mice(P<0.05), with no significant difference in LR change between Asthma+VitD3and Asthma+AS group mice. Compared to the Ctrl group, TNF-α, IL-1β, and IL-18 levels in BALF, as well as NLRP3, Caspase-1, and ASC protein expression levels in lung tissue, increased in the Asthma, Asthma+VitD3, and Asthma+AS group mice(P<0.05). Compared to the Asthma group, the Asthma+VitD3and Asthma+AS group mice showed decreased levels of the mentioned inflammatory factors in BALF and reduced protein expression of NLRP3, FOXO1, Caspase-1, and ASC in lung tissue(P<0.05). Compared to the Asthma+VitD3group, the Asthma+AS group showed increased FOXO1 protein expression(P<0.05), with no statistically significant differences in the other measured indicators. Conclusion VitD3can alleviate asthma symptoms induced by OVA in mice, improve the degree of airway inflammation, and reduce oxidative stress levels. The mechanism may be related to the downregulation of the FOXO1/NLRP3 axis.