To study the effect and mechanism of the combination of cycloheximide (Cyc) and total flavonoids from Dracocephalum moldevica (TFDM) on mice with pulmonary fibrosis (PF).Fifty C57BL/6 mice were randomly divided into five groups of 10 mice each according to body weight,namely,normal group,model group,TFDM group (360 mg/kg),Cyc group (5 mg/kg) and TFDM group (360 mg/kg)+Cyc group (5 mg/kg).A mouse pulmonary fibrosis model was constructed using intratracheal drip bleomycin (4 mg/kg),and the normal control group was given equal amounts of distilled water,and after the second day of modeling,the corresponding drug was given for 28 consecutive days.After the final dose,lung function tests were performed using the AniRes2005 animal lung function analysis system.The lung tissues were removed for HE staining to observe the degree of inflammation and Masson staining to observe the degree of fibrosis.The hydroxyproline (HYP) content of lung tissues was determined by hydrolysis.The expression of collagen Type 1 (Col-1),fibronectin (FN1),α-Smooth muscle actin (α-SMA),SHH,Ptch1,SMO,Gli1 and SUFU proteins in each group of mice were detected by Western blot.Compared with the blank group,HE staining showed abnormal lung tissue structure and inflammatory cell infiltration in the model group.Masson staining showed more collagenous fibrotic tissue stained blue and severe lung tissue damage.HYP content was significantly higher (P<0.01).Pulmonary function tests showed significantly higher inhalation phase airway resistance of lung (RL),expiratory phase airway resistance of expiration (RE) and FEV0.1/FVC and significantly lower significant increases in respiratory dynamic compliance (Cdyn),force vital capacity (FVC) and peak expiratory flow rate (PEF) (P<0.01).The results of Western blot showed that the lung tissues of model group showed elevated expression levels of Col-1,FN1, α-SMA,SHH,Ptch1,SMO and Gli1 proteins and significantly reduced expression levels of SUFU protein (P<0.01).Compared with the model group,the normal lung tissue structure and reduced inflammatory cell infiltration in the Cyc group and TFDM groups.Less blue fibrous tissue and remission of fibrosis in the lung tissue as evidenced by Masson staining.HYP content was upregulated (P<0.01).Pulmonary function tests showed significant decreases in RL,RE and FEV0.1/FVC and Cdyn and FVC and PEF (P<0.01).Western blot showed that the expression levels of Col-1,FN1,α-SMA,SHH,Ptch1,SMO and Gli1 proteins were significantly downregulated and the expression level of SUFU protein was significantly increased in lung tissues of mice with PF (P<0.01).TFDM can improve mouse PF to some extent,further concluding that the combination of Cyc and TFDM works better.