Biological macromolecular drugs, such as antibodies and fusion protein drugs, have been widely employed for the treatment of various diseases. Administration routes are typically via invasive intravenous or subcutaneous injection with needles; the latter is challenging for applications involving inflamed skin (e.g., psoriasis) due to concerns of expansion of inflammation. As a method of non-invasive transdermal drug delivery, we previously demonstrated that iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm2) enables transdermal permeation of hydrophilic macromolecules, such as small interfering RNA and nanoparticles into the skin, and subsequent exertion of their functions. The underlying mechanism was revealed to be via intercellular junction cleavage by cellular signaling activation initiated by Ca2+ influx. Based on these findings, in the present study, we hypothesized that non-invasive intradermal delivery of biological macromolecular drugs could be efficiently achieved via IP. Fluorescence of FITC-labeled IgG antibody was broadly observed in the skin after IP administration (0.4 mA/cm2 for 1 h) and extended from the epidermis to the dermis layer of hairless rats; passive antibody diffusion was not observed. In imiquimod-induced psoriasis model rats, antibodies were also delivered via IP into inflamed skin tissue. Additionally, upregulation of interleukin-6 mRNA levels, which is related to pathological progression of psoriasis, was significantly inhibited by IP of the anti-tumor necrosis factor-α drug etanercept, but not by its subcutaneous injection. Importantly, IP administration of etanercept significantly ameliorated epidermis hyperplasia, a symptom of psoriasis. Taken together, the present study is the first to demonstrate that IP can be applied as a non-invasive and efficient intradermal drug delivery technology for biological macromolecular drugs.