Exposure of fully differentiated 3T3-L1 adipocytes to 5 nM interleukin 11 (IL-11) resulted in an increase (1.9±0.5 fold) in the protein content for the heterotrimeric G protein Gαi2. This G protein has been suggested to be involved in the control of the insulin responsive glucose transporter (GLUT4) translocation to the plasma membrane. Conversely, IL-11 had no effect on the content of three other G proteins, involved in insulin action. The alteration in Gαi2 protein corresponds to and provides a molecular rationale for our previously described IL-11 induced increase in plasma membrane glucose transporter content and increased rate of glucose transport. In addition, treatment with the cytokine altered the protein content of several transcription factors, C/EBPα and CHOP-10 decreased while PPARγ and C/EBPβ increased. These changes in transcription factor content are consistent with an alteration of phenotype with the cells reverting to an earlier stage of the differentiation process in response to IL-11.