Opening the transdermal route to large hydrophilic drugs is one of the major challenges in the field oftransdermal drug delivery.Here we report that a short synthetic 11-mer peptide, identified through in vivo phage display, facilitated efficient transdermal protein drug delivery through the intact skin.Co-administration of the peptide and insulin in a saline solution to the exposed abdominal skin of stractozocin-induced diabetic rats resulted in elevated systemic levels of insulin and suppressed serum glucose levels for at least 11 hours.High systemic bioavailability of human growth hormone was also achieved transdermally when topically co-administered with the peptide.The peptide exhibits high sequence specificity as several single amino acid substitutions abolished its transdermal-enhancing activity.The peptide enabled penetration of FITC-insulin and b-galactosidase into hair follicles beyond 600 um depth.Time-laspe studies indicated that the peptide created a transient opening on the skin barrier to enable macromolecular drugs to reach the systemic circulation, possibly through the transfollicular route.