© 2021 Marmara University Press.The aim of this work was to develop colloidal nanocarriers for skin delivery of etodolac (ETD), which is a non-steroidal anti-inflammatory drug orally used for the management of acute pain and inflammation, but leads to unfavourable effects on the stomach. The oleic acid and blend of Labrasol/Trancutol P were used as oil phase and surfactant/co-surfactant mixture in the microemulsion formulations, respectively. ETD loaded microemulsions selecting the microemulsion region of pseudo-ternary phase diagrams were prepared, and then the microemulsions were characterised to confirm formation of oil in water microemulsions via optical isotropy, refractive index, droplet size, electrical conductivity, rheological behaviour and morphological analysis. In vitro permeation of ETD through porcine skin was evaluated using Franz diffusion cells for stable ETD loaded microemulsions. ATR-FTIR spectroscopy analysis was performed to elucidate interaction between the microemulsion components and stratum corneum structure on the molecular level. Confocal laser scanning microscopy analysis was further carried out to visualize skin penetration enhancement effect of the microemulsion formulation consisting of a model lipophilic fluorescent marker, Nile Red. The results indicated that the developed microemulsion formulation consisting of oleic acid, Labrasol, Transcutol P and water offer a potential approach to enhance skin delivery of ETD for topical treatment of inflammatory diseases.