Beside their function as static cells in hemostasis and thrombus formation platelets are mobile and able to migrate. In vitro transwell experiments identified the inflammatory chemokine stromal-derived factor-1 (SDF-1) as a potent mediator of platelet transmigration through porous membranes and interleukin 1b (IL1b)-inflamed endothelium, a process which involves phosphoinositol-3 kinase (PI3K) signaling. Transwell experiments showed that SDF-1-mediated platelet migration depends on the activity of different ion channels. Calcium channel blockers (2-APB, SKF) as well as a blocker of the calcium-dependent potassium channels (Clotrimazol) dramatically decreased platelet migration in response to SDF-1. The PI3K/PDK-1 downstream effector serum- and glucocorticoid-inducible kinase 1 (SGK1) is a powerful regulator of ion channels. The present study explored the role of SGK1 in the regulation of migration. Western blot analysis revealed that SDF-1 (200 ng/ml) treatment of platelets is followed by SGK1 phosphorylation at ⁴²²Ser, which leads to kinase activation. In transwell experiments migratory activity following stimulation with SDF-1 was significantly lower in platelets from SGK1 deficient mice (sgk1^-/-) than in platelets from their wild type littermates (sgk1^+/+). In vivo transmigration experiments in mice using intravital microscopy showed platelet invasion into post-ischemic vascular areas, which was significantly more pronounced in sgk1^+/+ than in sgk1^-/- mice. In conclusion, SGK1 is a powerful regulator of platelet migration into areas of vascular inflammation.