Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by fibroblasts proliferation and extracellular matrix (ECM) deposition, which lead to distorted lung architecture and function, as well as respiratory failure.Despite extensive research efforts, effective therapies are still limited.Recent studies show that the TGFβ/Smad signaling, as well as highmobility group box1 (HMGB1), could induce epithelialmesenchymal transformation (EMT) of alveolar epithelial cells (AECs) in PF.However, their inner link in EMT has not been clarified.In the study, we found that TGFβ1 could promote the proliferation of fibroblasts and HMGB1 induced EMT of A549 and RLE6TN cells by activating TGFβ1/Smad2/3 signaling.Furher study revealed that total glycosides of Yupingfeng (YTG), the extract from Yupingfeng san, one kind of traditional Chinese medicine prescription, could attenuate bleomycininduced PF in rats by inhibiting HMGB1 release.These findings further clarify the mechanisms of PF and provide alternative strategies for blocking the disease progression of PF by targeting HMGB1.