ABSTRACT The compound epigallocatechin gallate (EGCG) is one of several that have been reported to have insulin-like glucose-lowering properties in mammals. EGCG acts at least in part by repression of gluconeogenic genes including phosphoenolpyruvate carboxykinase (PEPCK) but the transcription factors that are targeted by EGCG were unclear until recently. We have found that EGCG mimics insulin-induced phosphorylation of the transcription factor FOXO1a. Like insulin, EGCG induced FOXO phosphorylation is abolished by PtdIns 3-kinase inhibition but not by PD98059 (an inhibitor of mitogen-activated protein kinase cascade) or by rapamycin (an inhibitor of signalling to p70 S6 kinase). In contrast to the effects of insulin and IGF-1 however, EGCG-mediated induction of FOXO phosphorylation is sensitive to scavengers of reactive oxygen species (ROS). The mechanism of action of EGCG and other insulin mimics is discussed. Our results suggest that agents that act on the same target(s) as EGCG may be useful antidiabetic agents.