【Abstract】Objective: To investigate the effects of Penequinine hydrochloride on tumor necrosis factor-alpha(TNF-α) and inducible nitric oxide synthase (INOS) expression in endotoxemia rats ,and the effects on nuclear factor kappa B(NF-KB) expression in the lung tissue of these rats.Methods: Sixty healthy SD rats were randomly divided into 5 groups ：control group（group C）；LPS group and P1～3 groups .endotoxemia was induced by intraperitoneal lipopolysaccharide (LPS) 8mg/kg in LPS group ,P1～3 groups Penequinine hydrochloride was infused intraperitoneal at 5 min before LPS administration in P1～3 groups.The animals were killed at 6 h later.The levels of TNF-α in blood samples were determined by using enzyme linked immunosorbent assay(ELISA),the levels of INOS activity in blood samples (by colorimetry),The expression of NF-KB p65 in the right lung tissue was detected by using Western blotting,The morphological changes of lung were inspected by means of optical microscope.Results: compared with control group,TNF-α content、iNOS activity in rat serum samples and NF-κBp65 protein expression in the lung tissue were significantly increased (P<0.05) ;compared with LPS group ,the expression of TNF-α ,and the iNOS activity,and the NF-κBp65 protein expression were significantly reduced in group P2 and P3 ,But group 1 had no significant difference;There Was no significant difference in the indices mentioned above among group P2 and group P3;The inflammatory responses was significantly ameliorated in group P2 and P3 as compared to LPS group .Conclusion: Penequinine hydrochloride can inhibit endotoxin-induced systemic inflammatory response by blocking TNF-α、NF-κBp65 uncontrolling release and reducing iNOS activity．