AbstractInterleukin 11 (IL‐11) is an anti‐inflammatory cytokine with receptors located on most cell types and tissues throughout the body. Its anti‐inflammatory properties are mediated through suppression of cytokine synthesis, in large part by prevention of NF‐κB activation. As adipose tissue synthesizes and secretes cytokines involved in establishing insulin resistance and due to the ability of IL‐11 to suppress cytokine synthesis, we initiated an investigation to determine the signal transduction pathways initiated by IL‐11 in adipose tissue. Using the 3T3‐L1 adipocyte cell culture model we demonstrate the rapid activation of the p44/42MAP kinase, PI3‐kinase, and STATs 1 and 3. Activation of MAP kinase is demonstrated to lead to the downstream activation of p90 RSK (ribosomal S6 kinase) as well as ATF‐1 and CREB. PI3‐kinase appears to activate the downstream target of p70 S6 kinase resulting in phosphorylation of ribosomal protein S6. STAT phosphorylation appears to be initiated through PI3‐kinase and to a lesser degree through p44/42 MAP kinase. These studies demonstrate the activation of three major signaling pathways and support a role for IL‐11 in the regulation of both transcription and protein synthesis in fully differentiated adipocytes. © 2005 Wiley‐Liss, Inc.