Background and purpose: Transcranial direct current stimulation (tDCS) is a neuromodulatory approach that deliver low-intensity of direct current to cortical areas inhibiting or facilitating spontaneous neuronal activity. In the last few years, tDCS has been intensively investigated for the treatment of several neurological conditions, including central nervous system (CNS) drug delivery strategy. However, the blood brain barrier (BBB) is a major hurdle for potential "would-be" CNS drug delivery. We thus ought to investigate whether different stimulation protocols could be beneficial in increasing the blood brain barrier permeability. Methods: The influence of both anodal and cathodal transcranial direct current stimulation was applied in normal rat. Rat were randomized and divided into three groups according to the treatment: anodal-tDCS, cathodal-tDCS and sham-tDCS. The active electrode was directly fixed onto the cranium while reference electrode was placed onto the ventral thorax. Direct electrical was applied using a current-constant stimulator to deliver a current of 500 µA for 30 min. Rat were then injected with Evans blue dye, sacrificed 1.5 h later, and perfused transcardially. Brains were removed, fixed and sectioned for histological analysis. Brain edema, water content as well as BBB integrity, were analyzed. Results: Evans blue fluorescence intensity was higher in the brain parenchyma of cathodal-treated rat compared to anodal- and sham-treated groups. Taken together, no significant brain edema was observed by histological staining. Conclusion: Our data indicate that transcranial direct current stimulation exerts a promising effect on the blood brain barrier permeability without causing brain edema. Pretreatment with tDCS may be a feasible technique to facilitate drug delivery into the CNS.