Pulsed electric field has been used widely to improve drug and gene delivery. The technique has different names. For gene delivery, it has been referred to as electroporation, electrogene transfer, and electrotransfection. Compared to other methods of gene delivery, electrotransfection is relatively safe and easy to use. However, its efficiency is low and unstable, partly because mechanisms of electrotransfection are complicated and remain to be fully understood. We discovered that the efficiency could be significantly reduced through knockdown of genes related to endocytic pathways or treatment of cells with endocytosis inhibitors, suggesting that endocytosis is involved in electrotransfection. We are currently investigating different approaches that can enhance intracellular transport of electrotransfected plasmid DNA.