Insulin is globally required to treat diabetes patients by an injection into the subcutaneous tissue, the fat layer under the skin, but this may cause pain or discomfort to patients. To avoid these issues, insulin delivery through a transdermal patch is an alternative choice for sustained insulin delivery. The porous thermoplastic polyurethane (TPU) was successfully fabricated as the drug matrix via solvent casting and a particulate leaching technique by using Triton X-100 as a porogen. The pore size of the porous TPU matrices increased with increasing Triton X-100 content, whereas the porosity was not visible in the dense TPU. The in-vitro drug release and in-vitro skin permeation were investigated by using Franz diffusion cells and insulin as the model drug. The experiment was carried out under the effects of pore sizes, pHs, and electric fields. The insulin released amount depended on the matrix pore size and electric field strength. The higher insulin released amount and higher insulin diffusion coefficient were obtained mainly due to the electro-repulsive force between the drug and the electrode. Pig skin was used as the membrane to mimic human skin. The lower insulin permeation amounts and lower insulin diffusion coefficients were obtained as the pig skin possessed a stratum corneum layer acting as an insulin barrier. Both the amount and diffusion coefficient were enhanced under an applied electric field. Therefore, the porous TPU matrix has been shown here to have potential as an insulin matrix for the transdermal patch under iontophoresis.