The glucoregulatory activities of ginsenosides compound K (CK) and Rg1 were investigated in 3T3-L1 adipocytes. Both compounds significantly enhanced glucose uptake in 3T3-L1 adipocytes in a dose-response manner, which is correlated with increased GLUT4 translocation from intracellular vesicles to the plasma membrane in adipocytes. The stimulating effects of CK and Rg1 on glucose uptake and GLUT4 translocation are associated with activation of AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways; both are key pathways in mediating glucose uptake in animal cells. In addition to the acute stimulus effect of glucose uptake, prolonged incubation of CK and Rg1 significantly induced GLUT4, but not GLUT1, expression at both the mRNA and protein levels in 3T3-L1 adipocytes. Further studies showed that CK inhibited and Rg1 enhanced triglyceride accumulation in adipocytes, suggesting that the mechanism of action of these ginsenosides may not be completely identical. In summary, this study demonstrated insulin-like activities of CK and Rg1 in adipocytes. These findings are important in understanding the hypoglycemic properties and potential applications of ginseng and ginsenosides.