Lipopolysaccharide (LPS) is known to produce several central and neuroendocrine effects and some of these effects are believed to be mediated through cytokines and other proteins. One such protein, leptin, produced by adipose tissue has been shown to cause anorexia, a central effect associated with LPS treatment. This raised the possibility that LPS-induced effects on feeding behavior may be mediated through leptin. This study was done to investigate the effects of systemic administration of LPS on plasma leptin levels in rats and the possible involvement of interleukin-1 (IL-1) in this mechanism. Adult male rats were implanted with indwelling jugular catheters and after collecting two pretreatment blood samples, the animals were injected (i.p.) with saline, 5 microg, 10 microg, or 25 microg/kg BW of LPS, or treated with 25 microg of soluble IL-1 receptor (sIL-1R) 5 min before and 90 min after 25 microg/kg BW of LPS. Posttreatment blood samples were collected at 30 min intervals for a period of 6 h. Plasma leptin concentrations were measured by radioimmunoassay. Treatment with saline did not produce any change in plasma leptin levels. In contrast, each of the three doses of LPS produced a dose-dependent increase in plasma leptin levels within 120 min. Leptin levels remained elevated for the next 4 h. Treatment with sIL-1 R completely blocked the LPS-induced increase in leptin levels, indicating that this effect is in fact mediated through IL-1. These results indicate that leptin could be a possible mediator of LPS-induced effects on feeding.