In conclusion, our study showed that the delivery of HYAP via ISI ameliorated bleomycin-induced pulmonary fibrosis compared to oral positive drugs, which was associated with blocking the activation of p38 in the MAPK-p38 signaling pathway and reducing the content of Smad3 in the TGF-β/Smad signaling pathway, which in turn decreased the levels of relevant inflammatory factors and ameliorated the effects of pulmonary fibrosis. Here, TGFB1 is linked to pulmonary fibrosis.