Chemerin, an 18 kDa protein secreted by adipose tissue, was reported to modulate immune system function through its binding to the chemerin receptor (chemerinR). We herein demonstrate that chemerin also influences adipose cell function. Our data showed that chemerin and chemerinR mRNA expressions were highly expressed in adipose tissues, and that their expression levels were up-regulated in mice fed a high-fat diet. Both chemerin and chemerinR mRNA expression dramatically increased during the differentiation of 3T3-L1 cells and human preadipocytes into adipocytes. Furthermore, recombinant chemerin induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK 1/2) and lipolysis in differentiated 3T3-L1 adipocytes. Thus, the adipokine chemerin likely regulates adipocyte function by autocrine/paracrine mechanisms.