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Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.