The ob gene product, leptin, is known to be an important circulating signal for regulation of food intake and body weight. We report here that peripherally applied leptin increased interleukin-1 receptor antagonist (IL-1ra) transcripts in the hypothalamus. Interestingly, we observed leptin-induced increase in IL-1ra transcripts not only in the hypothalamus but also in other brain regions such as the hippocampus, the cortex, the cerebellum, and the brain stem. Moreover, leptin applied to the db/db mice, which lack functional Ob-Rb receptor, increased IL-1ra mRNA levels in the hyothalamus to a similar extent as in normal mice. These results indicate that the leptin-induced IL-1ra expression in the brain may be mediated through STAT3 independent mechanisms. (C) 2002 Elsevier Science (USA). All rights reserved.