Objective To investigate whether the recombinant pyrin domain protein can alleviate the airway inflammation and airway remodeling of OVA-induced mice with chronic asthma by inhibiting transforming growth factor β1(TGF-β1)/SMAD and Jagged1/Notch1 signaling pathways. Methods Thirty-two male BALB/c mice were selected and divided into 4 groups with 8 mice in each group. The four groups were the control group, OVA model group, recombinant pyrin domain protein treatment group (100 μg/kg), and the dexamethasone treatment group (1 mg/kg). Enzyme-linked immunosorbent assay (ELISA) was used to determine the expression of inflammatory factors in bronchoalveolar lavage fluid (BALF) of mice in each group. hematoxylin-eosin staining (HE) was used to observe the inflammatory infiltration of bronchus in mice. The changes of goblet cells were observed by periodic acid-Schiff (PAS) staining and collagen fibers by Masson staining. Immunohistochemical staining (IHC) was performed to observe the expression distribution of α smooth muscle actin (α-SMA), TGF-β1 and Notch1 proteins in lung tissues. Western blotting was used to detect the protein levels of α-SMA, E-cadherin, TGF-β1, SMAD2/3, SMAD7, Jagged1, Notch1 and Hes1 in lung tissues. Results The recombinant pyrin domain protein not only improved the airway inflammatory response of the OVA-induced mice with bronchial asthma, but also inhibited the hyperplasia of goblet cells and collagen fiber deposition, reduced the tumor necrosis factor α (TNF-α) in BALF, interleukin 1β (IL-1β), IL-4, IL-13 levels, and inhibited the protein expression of TGF-β1, SMAD2/3, Jagged1, Notch1, Hes1 and α-SMA in lung tissues. Conclusion The recombinant pyrin domain protein can reduce the airway inflammation and airway remodeling of asthmatic mice by inhibiting TGF-β1/SMAD and Jagged1/Notch1 signaling pathways.