The purpose of this study was to explore the effect of lipid extraction by the simple alkyl acetates of increasing carbon chain lengths (e.g. methyl, ethyl, propyl, butyl, pentyl, hexyl, and octyl acetates) and iontophoresis on the in-vitro transport of leuprolide acetate through porcine epidermis. The extent of lipid extraction from the stratum corneum (SC) by alkyl acetates was studied by Fourier transform infrared (FT-IR) spectroscopy. Ethyl, propyl, pentyl, hexyl, and octyl acetates significantly increased (P<0.05) the permeability of leuprolide acetate through the epidermis in comparison to the control (epidermis without alkyl acetate treatment). Iontophoresis further increased (P<0.05) the permeability of leuprolide acetate for all the alkyl acetates studied, when compared to their corresponding passive permeability. Ethyl acetate produced the maximum passive (13.47 μg/cm 2 /h) and iontophoretic (89.79 μg/cm 2 /h) flux among all the alkyl acetates studied. The SC treated with alkyl acetates showed a decrease in peak heights and areas of asymmetric and symmetric C H stretching absorbances in comparison to untreated SC. A greater percentage decrease in peak heights and areas was obtained by ethyl acetate. Chloroform:methanol(2:1) [C:M(2:1)] was used as a positive control for lipid extraction. Our findings provide evidence that alkyl acetates cause lipid extraction, which leads to an enhancement in the passive and iontophoretic permeability of leuprolide acetate.