We assessed the time course effects of lipopolysaccaride (LPS) on food intake, cytokines, and hormones in rats and evaluated the relation between LPS-induced anorexia and its possible causative factors. Food intake was reduced 2 h after LPS injection (500 microg/kg, intraperitoneally) and remained decreased for 24 h. Plasma TNF-alpha and IL-6 levels increased by LPS administration at 0.5 and 2 h, and at 2 and 4 h, respectively. Plasma leptin and glucose levels were elevated at 8 and 16 h, and insulin levels were elevated at 2, 4, 8, and 16 h in the LPS-injected group, as compared to the counterpart controls. IL-6 levels in the CSF were elevated at 2 and 4 h. Hypothalamic cytokines tended to increase as early as 0.5 h after LPS injection and remained increased until 16 h. LPS-induced anorexia was attenuated in insulin-deficient STZ rats and was abolished by insulin treatment. The hypothalamic expression of NPY, a target of insulin's anorexic effect, was decreased 2 h after LPS administration, and central NPY injection (3 nM) prevented LPS-induced anorexia. In conclusion, cytokines, insulin, and leptin levels evidence different time courses by LPS administration. In LPS-induced anorexia, insulin may constitute a newly found causative factor, whereas leptin appears to be uninvolved in an early period in rats.