To observe the effects of melittin on inhibiting pulmonary fibrosis induced by bleomycin in rats. Methods:Seventy SPF grade C57BL/6 rats were randomly divided into the normal group(n=10)and the model group，dexamethasone group and melittin low dose group，melittin middle dose group and melittin high dose group(n=12). In addition to the normal group，a rat model of pulmonary fibrosis was prepared by injecting bleomycin(BLM)into the trachea. From the first day after surgery，the dexamethasone group was intraperitoneally injected at a dose of 3 mg/kg，while the low，medium and high doses of melittin were administered to 5，10，and 20 μg/(kg·d） respectively. The control group and the model group were given an equal volume of saline for 2 weeks. The animals were sacrificed on the 7th and 14th day，respectively，peripheral blood samples of which were collected. ELISA was used to detect serum transforming growth factor(TGF-β1)，collagen I(Collagen I)，collagen III(Collagen III)，and matrix metalloproteinase 2(MMP2)and the level of matrix metalloproteinase 9(MMP9). Lung tissue was taken for hematoxylin-eosin(HE)analysis，Masson staining and hydroxyproline(HYP)evaluation to observe histopathological changes and collagen deposition. The expressions of TGF-β1，Smad2，Smad3 and other proteins and genes in lung tissue of each group were observed by Real-time PCR and Western blot. Results:Compared with the control group，the pulmonary fibrosis was significantly increased in the model group. The contents of HYP，TGF-β1，Collagen I and Collagen I were increased(P<0.05)，and the expression of TGF-β1，Smad2，Smad3 protein and gene in lung tissue was increased(P<0.05); Compared with the model group，the levels of serum HYP，TGF-β1，Collagen I，CollagenI in the high dose group of melittin decreased(P<0.05)，and TGF-β1，Smad2，Smad3 protein in lung tissue and gene expression was decreased(P<0.05). There was no statistically significant difference in the low-dose group. Conclusion:Melittin can effectively reduce the degeneration of pulmonary fibrosis induced by bleomycin，and its mechanism may be related to the regulation of TGF-β1/Smads pathway.