The aim of this study was to prepare a microemulsion based hydrogel containing sesame oil and evaluate itstopical application in preventing the harmful effects of UV radiation on the guinea pig\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s skin using histo-pathologic and clinicalfindings. Sesame oil with high antioxidant content and unique chemical and physiolo-gical properties is a suitable candidate for the evolution of UV protection on skin. Applying this natural oil inmicroemulsion formulation containing particles with nanometer size can enhance its efficacy. To prepare astable microemulsion, it is necessary to select the appropriate surfactants. In this study,first the best combi-nation of hydrophilic surfactant of Tween 80 with various lipophilic surfactants such as Span 20, Span 80 andSpan 85 at different surfactant ratios was examined. The microemulsion formulations were assessed for particlesize, zeta potential, polydispersity index, refractive index, electrical conductivity, pH value and stability. Resultsshowed that among various samples, microemulsion containing a mixture of Tween 80 and Span 80 with thesurfactant ratio of 9:1 was the best sample in terms of stability over time -six months-. This sample had a lowerparticle size of 26.09 nm with a narrow particle size distribution. For topical application, the microemulsionbased hydrogel was prepared with 0.6% Carbomer 940 as a gelling agent. The pH value and viscosity of gelformulation were 6.6 and 12.90 Pa.s, respectively, which is appropriate for topical applications. A slight en-hancement of particle size inside hydrogel structure was observed after six months of the gel preparation. Theclinical evolutions of formulation on guinea pig\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s skin were included skin scaling, skin irregularity, erythema,skin hyperpigmentation, and edema. Epidermal hyperkeratosis, hyperpigmentation, exocytosis, acanthosis,chromatin discoloration in nucleus of epidermal squamous cells, perifolliculitis, dermal vascular hyperemia,edema and dermal thickness, infiltration of plasma cell lymphocytes and eosinophils into dermis were observedfor histopathological investigations. Based on clinical and histopathological examinations, topical application ofmicroemulsion-based hydrogel of sesame oil can effectively prevent skin damage induced by UV radiation and istherefore suitable for skin products.

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