Calcaratarin D (CalD), a labdane diterpenoid, has recently been shown to possess anti-asthma property in a mouse allergic asthma model. The present study evaluated the therapeutic effects of CalD in the context of pulmonary fibrosis including pro-fibrotic cytokine TGF-?1-induced epithelial-mesenchymal transition (EMT) and fibroblast activation. The effects of CalD on the biomarkers of TGF-?1-induced EMT in A549 airway epithelial cells and TGF-?1-activated normal human lung fibroblasts (NHLFs) were investigated. A bleomycin-induced pulmonary fibrosis model was also established for evaluation of the effects of CalD in vivo. In A549 cells, TGF-?1 induced an increase in N-cadherin and a decrease in E-cadherin, the hallmark of EMT. CalD reversed the alteration of N-cadherin and E-cadherin, and inhibited the expression of Snail and Slug, two pivotal transcription factors for EMT. In NHLFs, TGF-?1 stimulated the expression of extracellular matrix proteins collagens, myofibroblast marker ?-smooth muscle actin (?-SMA), and fibrinolysis inhibitor plasminogen activator inhibitor 1 (PAI-1). CalD suppressed the increased expression of collagens, ?-SMA and PAI-1 in NHLFs. Besides, a bleomycin-induced pulmonary fibrosis model was established by intratracheal administration of 3 mg/kg bleomycin for 21 days. Instillation of bleomycin promoted lung histopathological change and collagen deposition. Infiltration of immune cell and elevation of TGF-?1 were also observed in the bronchoalveolar lavage from bleomycin mice. Our results demonstrated that CalD could be a novel anti-fibrotic agent that warrants further investigation in bleomycin pulmonary fibrosis model.