Tangeretin and nobiletin are polymethoxyflavonoids that are contained in citrus fruits. Polymethoxyflavonoids are reported to have several biological functions including anti‐inflammatory, anti‐atherogenic, or anti‐diabetic effects. However, whether polymethoxyflavonoids directly affect glucose uptake in tissues is not well understood. In the current study, we investigated whether tangeretin and nobiletin affect glucose uptake in insulin target cells such as adipocytes. We observed that treatment with tangeretin or nobiletin significantly increased the uptake of [3H]‐deoxyglucose in differentiated 3T3‐F442A adipocytes in a concentration‐dependent manner. Data showed that phosphatidyl inositol 3 kinase, Akt1/2, and the protein kinase A pathways were involved in the increase in glucose uptake induced by polymethoxyflavonoids. These data suggest that the anti‐diabetic action of polymethoxyflavonoids is partly exerted via these signaling pathways in insulin target tissues. Copyright © 2012 John Wiley & Sons, Ltd.