Insulin loaded microneedles were prepared using dextrin as the base for the percutaneous administration of insulin. Under room temperature, insulin solution was added to high concentration of dextrin solution, glue, and microneedles were prepared by forming thread with polypropylene tips. The mean weight of the microneedles was 0.59+/-0.01 (S.E.) mg. The mean length and basal diameter were 3.24+/-0.16 and 0.55+/-0.03 mm, respectively. Five microneedles were percutaneously administered to mice at the insulin dose levels of 0.5, 1.0 and 2.5IU/kg. After administration, blood samples were collected for 5 h and plasma glucose levels were measured. Lowest plasma glucose level appeared at 1 h after the administration of microneedles and dose-dependent hypoglycemic effect of insulin was clearly observed in those dose range. By comparing the mean area above the plasma glucose level versus time curve (AAC) between microneedle preparation and i.v. solution, the pharmacological availabilities were calculated to be 97.7% (0.5IU/kg), 93.3% (1.0IU/kg) and 91.3% (2.5IU/kg), respectively. When highly loaded insulin loaded microneedle was administered to mice with one microneedle, there was not a significant difference on the plasma glucose level versus time curves between 5 and 1 microneedle experiments. In vitro release study showed that almost all of the formulated insulin was released within 1 h. The T50% was estimated to be 15.4+/-1.1 min. Stability of insulin in the microneedle preparations showed that the remaining insulin after 1 month of the storage were 98.2% (-80 degrees C), 98.9% (20 degrees C) and 99.0% (40 degrees C). Evans blue (EB) loaded microneedles were also prepared and histological study was performed with HWY-Slc hairless rats. The diffusion of EB from the microneedle to the environmental skin reached to the maximum at 3 h after administration. The scab was formed at 24 h after administration. The wound formed by the administration of microneedle was cured at 72 h after administration. Those results suggest the usefulness of a self-dissolving microneedle for the percutaneous delivery of peptide/protein drugs like insulin.