Muscle and fat cells facilitate glucose import by the glucose tranporter isoform GLUT4, a process under the tight control of the protein kinase B (PKB) which is activated by insulin. Similar to PKB, the serum and glucocorticoid inducible kinase (SGK) 1 is upregulated by insulin and was shown to be a potent regulator of diverse metabolite transporters. In this study, we evaluated the putative role of SGK1 in the modulation of GLUT4 activity and expression. Glucose uptake in adipocytes isolated from sgk1-/- mice was reduced compared to their wild-type littermates. Furthermore, coexpression of the kinase along with GLUT4 in Xenopus oocytes resulted in an increase of radiolabeled 2-deoxy- glucose uptake. The enhanced GLUT4 activity upon SGK1 was paralleled by increased transporter abundance in the plasma membrane. GLUT4 stimulation by the kinase was not caused by de novo protein synthesis. Coexpression of the inactive mutant K127NSGK1 failed to modulate both GLUT4 activity and expression, indicating that SGK1 is effective through phosphorylation. Disruption of the SGK1 phosphorylation site on GLUT4 (S274AGLUT4) abrogated the stimulating effect. In summary, SGK1 promotes glucose transport by enhancing GLUT4 abundance in the cell membrane at least in part via GLUT4 phosphorylation. The results suggest that SGK1 may contribute to the activation of glucose uptake by insulin.