Abstract Ghrelin, a circulating orexigenic hormone, exerts potent therapeutic effect in several models of inflammatory diseases, such as endotoxemic shock, ulcerative colitis and autoimmune encephalomyelitis. Suppression of production of pro-inflammatory cytokines from immune cells has been proposed as a mechanism of this effect of ghrelin. Here we report that ghrelin enhances lipopolysaccharide (LPS)-induced production of the anti-inflammatory cytokine IL-10 from human peripheral blood monocyte-derived macrophages. Interestingly, IL-10 production from LPS-activated monocytes was not affected by ghrelin. Further studies revealed that the ghrelin receptor, namely, growth hormone secretagogue receptor (GHS-R), is significantly upregulated during macrophage differentiation. Moreover, ghrelin enhanced expression of the transcription factor c-Maf essential for IL-10 gene expression in macrophages. Whether induction of c-Maf by ghrelin is responsible for the enhanced IL-10 production and the significance of IL-10 in overall anti-inflammatory action of ghrelin in vivo is currently under investigation.