We previously reported that a weak current (WC, 0.3-0.5 mA/cm2) applied to cells can induce endocytosis to promote cytoplasmic delivery of hydrophilic macromolecules (MW: <70,000), such as dextran and siRNA, which leak from WC-induced endosomes into the cytoplasm (Hasan et al., 2016). In this study, we evaluated the characteristics of WC-mediated endocytosis for application of the technology to cytoplasmic delivery of macromolecular medicines. WC induced significantly higher cellular uptake of exogenous DNA fragments compared to untreated cells; the amount increased in a time-dependent manner, indicating that endocytosis was induced after WC. Moreover, following WC treatment of cells in the presence of an antibody (MW: 150,000) with the lysosomotropic agent chloroquine, the antibody was able to bind to its intracellular target. Thus, high molecular weight protein medicines delivered by WC-mediated endocytosis were functional in the cytoplasm. Transmission electron microscopy of cells treated by WC in the presence of gold nanoparticles covered with polyethylene glycol showed that the WC-induced endosomes exhibited an elliptical shape. In the WC-induced endosomes, ceramide, which makes pore structures in the membrane, was localized. Together, these results suggest that WC can induce unique endocytosis and that macromolecular medicines leak from endosomes through a ceramide pore.