Objective To investigate the effect of penehyclidine hydrochloride on pulmonary interstitial fibrosis induced by paraquat in rats and it's possible mechanisms. Methodes Forty-eight male Sprague-Dawley rats were randomly divided into four groups, control group, model group, PHC group treated with penehyclidine hydrochloride and Dex group treated with dexamethasone, and every group was again randomly divided into 7th day and 22th day subgroup, there were 6 rats in every group. 20% paraquat (18mg/kg, diluted to 1ml) was injected peritoneally for poisoning model, while in the control group 1ml norrnal saline was used. 30 minutes after exposure to paraquat, rats in PHC group and Dex group were intraperitoneally injected with penehyclidine hydrochloride(0.1mg/kg), dexamethasone(3mg/kg), and then repeated injection once per 24h, all intervention drug were diluted to 1 ml with normal saline; rats in control group and model group at corresponding time points were given with equal volume of normal saline. On the 7th day and 22th day respectively, experimental animals were killed to detect the PaO2 and PaCO2, the lun wet / dry ratio (W/D), the pathological changes of lung tissue by HE staining and Masson staining, and the TGF-β1 expression in lung tissue with immunohistochemistry. Results The PaO2 was significantly lower , the PaCO2 , pulmonary W/D and TGF-β1 expression was significantly increased in rats exposured to paraquat。The morphological changes presented acute pulmonary inflammatiuon on the 7th day ,while on the 22th day, pulmonary fibrosis appeared. Penehyclidine hydrochloride and dexamethasone, could significantly increase PaO2, decrease PaCO2; inhibit lung inflammation infiltration , reduce pulmonary interstitial fibrosis; significantly reduce lung W / D and TGF-β1 expression in the lung tissue, and there were no obvious difference in PHC group and Dex group. Conclusion Penehyclidine hydrochloride can reduce lung inflammation infiltration and suppress the occurrence of pulmonary interstitial fibrosis of paraquat poisoning in rats by inhibitting the expression of TGF-β1.