Platelets have been shown to migrate and thus to invade the vascular wall. Platelet migration is stimulated by SDF-1. Migration is inhibited by vinculin. In other cell types, migration is dependent on Ca²⁺-entry via Ca²⁺-channels such as Orai1 and on the serum and glucocorticoid inducible kinase 1 (SGK1), which is a downstream effector of the PI3-K pathway and upregulates Orai1. Ca²⁺-influx is sensitive to cell membrane potential, which is maintained by K⁺-channel activity and/or Cl^--channel activity. The present study explored the role of ion channels and SGK1 in the regulation of SDF-1 induced migration. Platelets were isolated from human volunteers as well as from gene targeted mice lacking the Ca²⁺-activated K⁺-channel SK4 (sk4^-/-) or SGK1 (sgk1^-/-). SDF-1 stimulated migration in human platelets, an effect blunted by Orai-1 inhibitors 2-APB and SKF-96365, by unspecific K⁺-channel inhibitor TEA, by SK4 specific blocker clotrimazole, but not by Cl^--channel inhibitor NPPB. Stimulation of migration by SDF-1 was observed in sk4^+/+ andsgk^+/+ platelets but was absent in sk4^-/- and sgk1^-/- platelets. Phosphorylation of vinculin was enhanced in sgk1^-/- platelets. In vivo experiments in intestinal vessels after vascular inflammation revealed that transmigration of platelets into inflamed vessel walls was significantly less pronounced in sgk1^-/- than in sgk^+/+ mice. In conclusion, platelet migration requires activity of Orai1 and SK4, but not of NPPB-sensitive Cl^--channels. Furthermore SGK1 is crucially involved in the regulation of platelet migration.