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Macromolecular drugs, such as protein, peptides, antibodies, nucleic acids ect, have been recognized around the world as the future "drug-of-choice", due to their high specificity, good biocompatibility and high efficiency. However, their applications have been limited by the poor stability and cell permeability caused by the large molecular weight, varying surface charges and fragile structures. The discovery of cell penetrating peptide(CPP) shed light in solving the poor cell permeability problem. CPPs are short peptides that have the capacity to cross cellular membranes with very limited toxicity without the necessity of recognition by specific receptors. CPPs can transport inside living cells a variety of covalently or non-covalently linked cargoes, including peptides, proteins, nucleic acids, nanoparticles and liposomes. This talk will highlight several cell penetrating peptide mediated drug delivery systems for macromolecular therapeutics, including antibody targeted CPP-siRNA delivery system, fusion protein self-assembled fluorescent nanoprobe and protein delivery system, oral insulin delivery system.