Pulmonary fibrosis is the final outcome of a variety of diffuse pulmonary interstitial diseases, and it has an unclear pathogenesis. There is no effective drug treatment, so the clinical prognosis is poor. As an effective component of ginseng, total ginsenoside (TG) inhibits acute lung injury. This study determined whether TG has protective effects on pulmonary fibrosis and investigated its protective mechanisms. A pulmonary fibrosis model in BALB/c mice was established by injecting the bleomycin chemotherapeutic agent into the trachea. TG (40, 80, and 160 mg/kg/d) was given continuously for 28 days from the second day after development of the model. Pulmonary fibrosis was determined by measuring the lung coefficient, haematoxylin and eosin, and Masson’s trichrome staining of lung samples, and detection of alpha smooth muscle actin expression in lung tissues. To investigate the mechanisms of anti-pulmonary fibrosis by TG, we detected the genes and proteins of the transforming growth factor-β1 (TGF-β1)/Smad signalling pathway and matrix metalloproteinase (MMP) system. Treatment with TG (40, 80, and 160 mg/kg/d) ameliorated pulmonary fibrosis induced by bleomycin in mice, downregulated the expression of TGF-β1, Smad2, Smad3, MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1, and upregulated the protein expression of Smad7. These results suggest that the protective effects of TG on pulmonary fibrosis induced by bleomycin are related to regulation of the TGF-β1/Smad signalling pathway and MMP system.