Granisetron Hydrochloride is a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist used for the prevention and treatment of nausea and vomiting associated with cancer chemotherapy. Based on the hydrophilicity of this drug (pka=9.4) it is unlikely that passive diffusion across the skin could deliver therapeutic amounts from a large sized patch. This study was conducted to evaluate the feasibility of in vitro transdermal delivery of granisetron using electroporation across full thickness hairless rat skin. A 2 4-1 fractional factorial design was used to determine the most important variables affecting the transdermal delivery of granisetron using electroporation. The variables studied and respective levels investigated were drug concentration (10, 20 mg/ml), voltage (155, 310 volt), pulse duration (12, 24 ms) and number of pulses (100, 200 pulses). Permeation profiles were used for the representation of data, where Q: the cumulative amount permeated per cm 2 (µg/cm 2) was plotted against time (min). The selected dependent variable (response) was Q120 which is the cumulative amount permeated per cm 2 after 2 hours. Design-expert version 7.0.0 was used for the statistical evaluation. The results of the analysis of variance (ANOVA) revealed that Q120 was significantly affected by the voltage, pulse duration and number of pulses. The drug concentration had a non significant effect on Q120. A reduced polynomial regression equation which expresses the influence of process parameters on the response was obtained to enable navigation of the experimental space.