The acute reactions of human skin to solar ultraviolet radiation (290-400 nm) are recognized as a form of inflammation reactions that are mediated by several possible mechanisms including (a) direct action of photons on DNA, (b) generation of reactive free radicals and reactive oxygen species involving the formation of O2.-, 1O2, H2O2, OH, etc., (c) generation of prostaglandins (PGD2, PGE2, etc.), histamine, leucotrienes, and other inflammatory mediators. It is conceivable that UV-induced reactions represent oxidative stress mediated by the formation of free radicals, reactive oxygen, lipid peroxidation, liberation of membrane phospholipids, and subsequent formation of prostaglandins by cyclo-oxygenase pathway. In this study, we examined the role of reactive oxygen species and lipid peroxidation in in vitro reactions as well as in vivo skin inflammation reactions induced by (a) UVB radiation (290-320 nm), and (b) skin photosensitization reaction by PUVA treatment involving 8-methoxypsoralen and UVA (320-400 nm) radiation and presented data for the generation of superoxide anion O2.-) and lipid peroxides. We have also evaluated, both in vitro as well as in vivo systems, the quenching or the inhibition of O2.- by a plant extract known as Polypodium leucotomos. The P. leucotomos extract was found to exhibit interesting antioxidant and anti-inflammatory as well as photoprotective properties against photo-oxidative stress involving the generation of reactive oxygen, lipid peroxidation under in vitro reactions as well as in vivo experimental conditions. Significant inhibition of UVB-induced erythemal response, and 8-methoxypsoralen plus UVA-induced phototoxic reaction after topical application or oral administration of the photosensitizer could be demonstrated in guinea pig skin and human skin following the topical application of P. leucotomos extract. The photoprotective mechanism of P.leucotomos involving interaction with reactive oxygen species or free radicals appears to have potential clinical usefulness in preventing sunburn and inhibiting phototoxic reaction.