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IL\u20106 binds to membrane\u2010bound IL\u20106 receptor \u03b1 (IL\u20106R\u03b1) (classic signaling) or soluble IL\u20106R\u03b1 (trans\u2010signaling); this complex then associates with the signal\u2010transducing membrane protein gp130. IL\u20106R\u03b1 and gp130 float on membrane (i.e., lipid) rafts; however, how membrane rafts regulate IL\u20106 signaling remains unclear. Here, we demonstrate that both IL\u20106 classic signaling and trans\u2010signaling depend on membrane cholesterol, an essential raft component. Super\u2010resolution fluorescence imaging using perfringolysin O D4 fragments that selectively bind to high cholesterol concentrations revealed that IL\u20106 and hyper\u2010IL\u20106, a fusion protein of IL\u20106 and soluble IL\u20106R\u03b1, induce the alteration of membrane rafts. IL\u20106 and hyper\u2010IL\u20106 induced D4\u2010positive raft (D4 raft) formation without affecting cholera toxin subunit B (CTB)\u2010positive rafts (CTB rafts). Receptor clustering of IL\u20106R\u03b1 and gp130 and STAT3 phosphorylation occurred in D4 rafts. These results indicate that D4 rafts serve as platforms for the assembly of functional IL\u20106 receptor complexes. We found that Eps15 homology domain\u2010containing protein 1 (EHD1) mediates the formation of functional IL\u20106 receptor complexes through D4 rafts. 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