Background: Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays a critical role in various organ fibrosis by promoting crosslink of the extracellular matrix proteins: collagen and elastin.Our previous study demonstrated that Epithelial-to-Mesenchymal Transition (EMT) was strongly associated with paraquat (PQ) induced pulmonary fibrosis.We wonder whether LOX has significance on EMT in the process of pulmonary fibrosis induced by PQ.Objective: To explore the relationship between LOX and EMT in the progress of pulmonary fibrosis induced by PQ poisoning.Methods: We utilized siRNA silencing by genetic approaches and inhibitor of LOX by protein approaches to inactivate LOX and then to observe changes in cell morphology and the degree of EMT induced by the PQ poisoning in vitro.By inhibiting the activity of LOX in rats to establish the vivo model of PQ poisoning with intraperitoneal injection of 3-Aminopropionitrile (BAPN) and to detect proteins expression associated with EMT, to take the lung tissue HE staining and to observe the degree of lung injury.LOX protein, mesenchymal marker α-SMA protein and epithelial marker E-cadherin or ZO-1 of EMT were measured by western blot.Results: We found cells had occurred EMT after PQ poisoning that epithelial-specific round or ellipse morphologies of RLE-6TN and A549 cells were disrupted and cells acquired a spindle-shaped morphology.LOX and α-SMA level were increased whereas E-cadherin level was decreased.Moreover, silencing of LOX attenuated the process of EMT, down-regulating α-SMA and LOX expression and up-regulating E-cadherin expression.These were consistent with the results from inhibiting the activity of LOX protein with inhibitor BAPN, Bathocuproinedisulfonic (BCS) in vitro.Inactivation of LOX in A549 cells gradually attenuated the process of EMT as the concentration of inhibitor increased.In addition, inhibition of LOX protein expression, the extent of the EMT of PQ poisoning rats were also reduced, the degree of inflammation and thickening of alveolar interval were significantly reduced than simple PQ poisoning rats by H&E staining.Conclusions: Our results indicate that LOX can promote the progress of EMT in PQ-induced pulmonary fibrosis and inhibition of LOX expression using siRNA and inhibitors alleviates PQ-induced EMT.