Here we characterized the proteins associated with detergent resistant membranes (DRMs) from resting and activated human platelets. We achieved a proteomic profile of 141 DRM proteins involved in many biological pathways including 'PAR-1-mediated thrombin signal events', 'Integrin family cell surface interactions', 'Platelet activation, signalling and aggregation' and 'Platelet degranulation'. Therefore, a high level of relevant platelet signalling and trafficking proteins were identified e.g., Rap 1b, Src, SNAP-23 and syntaxin-11, implicating platelet DRMs as concentrating platforms not only in the critical platelet function of activation but also in secretion/degranulation.