Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on NF-κB mRNA expression and SOD activity in lung tissues in rats with acute lung injury (ALI) induced by LPS.Methods Thirty-two male SD rats, 2 months old, weighing 230-280 g, were randomly divided into 4 groups (n=8 each): control group (group C), ALI group, low dose PHCD group (group LP) and high dose PHCD group (group HP). ALI was induced by intravenous LPS 5 mg/kg via tail vein. Group LP and HP received intraperitoneal PHCD 0. 3 and 1 mg/kg respectively 30 min before LPS administration. The rats were killed at 6 h after LPS administration. The lungs were removed immediately for determination of W/D lung weight ratio, lung water content, NF-κB mRNA expression, TNF-α and MDA content, and SOD activity and microscopic examination. Results NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly higher, while SOD activity was significantly lower in group ALI, LP and HP than in group C (P ＜ 0.05). NF-κB mRNA expression, TNF-α and MDA content, W/D lung weight ratio and lung water content were significantly lower, while SOD activity was significantly higher in group LP and HP than in group ALI and HP than in group LP (P ＜ 0.05). The LPS-induced changes were mitigated by pretreatment with low and high doses of PHCD in group LP and HP.Conclusion Pretreatment with PHCD attenuates LPS-induced ALI by downregulating NF-κB mRNA expression, decreasing local inflammatory response and enhancing anti-oxidant activity.