The electroporation technique has been used significantly to increase drug permeation through the skin. This technique relies on the application of short-timed (microseconds to millisecond) electric fields (generally, order of 50- 300 V) on the skin to create microscopic pores. However, the molecular mechanism of pore formation, resulting in an enhanced flux of active molecules through the skin, remains poorly understood. In this study, extensive atomistic molecular dynamics simulation of skin lipids [made up of ceramide (CER), cholesterol (CHOL), and free fatty acid (FFA)] has been performed at various external electric fields. We show for the first time the pore formation in the skin lipid bilayer during electroporation. We show the effect of the applied external electrical held (0.6-1.0 V/nm)on the pore formation dynamics in the lipid bilayer of different sizes (154, 616, and 2464 lipids) and compositions (CER/CHOL/FFA, 1:0:0, 1:0:1, 1:1:0, 1:1:1). The pore formation and resealing kinetics were different and were found to be highly dependent on the composition of the skin lipid bilayer. The pore formation time decreased with increase in the bilayer size. The pore sustaining electnc field was found to be in the range of 0.20-0.25 V/nm for equimolar CER, CHOL, and FFA lipid bilayers. The skin lipid bilayer (1:1 :l) sealed itself within 20 ns after the removal of the external electric field. We also present the molecular mechanism of enhancement of drug permeation in the presence of external field as compared to the passive diffusion. The molecular-level understanding obtained here could help in optimizing/designing the electroporation experiments for effective drug delivery. For a given skin composition and size of the drug molecule, the combination of pore formation time and pore growth model can be used to know a priori the desired electric field and time for the application of the electric field.