Objective To investigate the influence of melatonin(MT) on the expression of tumor necrosis factor alpha(TNF-α) in peripheral blood and vascular tissue of rats with endotoxemia induced by lipopolysaccharides(LPS) .Methods The male SD rats were divided into four groups:solvent control group;LPS group;LPS+MT group;MT group(5 mg/ml,i.p.) .The content of TNF-α in serum was detected by enzyme linked immunosorbent assay(ELISA) .The expression of TNF-αmRNA in vascular tissue was detected by RT-PCR and immunohsitochemistry.Results As compared with those in control group,the levels of TNF-α in serum and the expression of TNF-α mRNA in vascular tissue were significantly increased in LPS group(P0.01) ,and the expression of TNF-α protein in vascular endothelium and smooth muscle cells was increased,however,the MT intervention therapy before and after administrating LPS could obviously reduce the content of TNF-α in serum,and could decrease the production of TNF-α mRNA in blood vessel in LPS+MT group,as compared with those in LPS group at the same time point(P0.01) .Conclusion MT can inhibit the generation and expression of TNF-α in rats with endotoxemia.