〔Abstract〕 Abstract Objective To investigate the mechanisms of bromodomain-containing protein 4 (BRD4) in TGF-β1-in- duced epithelial-mesenchymal transition in alveolar type II epithelial cells . Methods MLE-12 cells were stimula- ted with different concentrations (5 ng/ml , 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model . The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1 , 100 μmol/L high mobility group box 1 protein (HMGB1)inhibitor glycyrrhizin acid (GA) , and 3 μg/ml rHMGB1 . The experimental groups were divided as fol- lows : control group , TGF-β1 group , JQ-1 group , JQ-1 + TGF-β1 group , GA group , GA + TGF-β1 group , and JQ - 1 + TGF-β1 + rHMGB1 group . The effect of JQ-1 on cell viability was examined using cell counting kit-8 ( CCK- 8) . The protein expression levels of CDH1 , ZO-1 , Vimentin , α-SMA , BRD4 , HMGB1 , TGF-β1 , Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test. Results Compared with the control group , the levels of Vimentin and α-SMA in the TGF-β1 group increased , and the levels of CDH1 and ZO-1 protein decreased , suggesting that the EMT model was successfully established . In this model , the expression of BRD4 and HMGB1 significantly increased . Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-in- duced EMT , and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1 . Moreover , rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway . Additionally , both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration , whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration . Conclusion BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1 /TGF-β1/Smad2/3 signa- ling cascade , and BRD4 may be a potential target for inhibition of pulmonary fibrosis .