Peripheral administration of bacterial lipopolysaccharide (LPS) and various inflammatory cytokines to rodents is known to raise plasma levels of leptin, a potent satiety factor secreted from adipocytes, implying a role of leptin in endotoxin-induced anorexia. We previously reported no effect of LPS on serum leptin levels in sheep, despite marked anorexia and fever. Our results suggest that leptin might not be involved in the endotoxin-induced anorexia in ruminants. To test this idea, in the present study, plasma leptin levels were measured during acute experimental endotoxemia in Holstein cows. Intravenous injection of LPS induced anorexia accompanied with increases in plasma levels of cortisol and insulin, all of which are known to stimulate leptin secretion in rodent and human, while it did not affect plasma leptin levels at all in cows. Similar results were also obtained after injection of recombinant bovine tumor necrosis factor alpha. These results indicate that plasma leptin levels in cows during acute endotoxemia are differentially regulated from those in rodents, and that leptin might not be involved in the endotoxin-induced anorexia in ruminants.