The effects of Ganoderma lucidum on glucose uptake was studied in L6 rat skeletal muscle cells. Glucose uptake in muscle cell was increased about 6-fold compared to control by mushroom extract treatment. This increasing effect to the glucose uptake was observed in muscle cells cultured with or without insulin. The levels of phosphor-acetyl CoA carboxylase were upregulated by G. lucidum extract treatment in insulinstimulated and basal culture conditions. However, G. lucidum extract did not affect protein kinaseB/Akt(Akt) level. Furthermore, the expression of phosphor-AMPactivated protein kinase(AMPK) was also up-regulated. AMPK is another regulatory protein in the glucose uptake pathway and energy metabolism. Thus, the treatment of G. lucidum extract in skeletal muscle cells increased the phosphorylation levels of AMPK and acetyl-CoA carboxylase, showing that the increase of glucose uptake by G. lucidum extract might be mediated via the activation of AMPK signaling pathway