The understanding of the anti-inflammatory mechanisms of action of plant polyphenols (PPs) and clarification of the relationship between their anti-inflammatory and antioxidant properties may result in a new therapeutic approach to skin cancers. To elucidate the underlying mechanism, we analyzed the ability of PPs to attenuate inflammatory, metabolic and oxidative cellular responses to UV irradiation. Normal human epidermal keratinocytes (NHEK) were exposed to physiologically relevant dose of solar-simulated UV irradiation. Effects of pre- and post-treatment with PPs on the overproduction of peroxides and inflammatory mediators (mRNA and protein) were analyzed using real-time RT-PCR, enzyme-linked immunosorbent and fluorometric techniques. Differences between the effectiveness of pre- and post-treatment with polyphenols was found. In particular, PPs post-treatment, but not pretreatment, completely abolished overexpression of Cyp1a1 and Cyp1b1 genes and elevation of intracellular peroxides in NHEK irradiated by UV. Post-treatment with PPs also more efficiently than pretreatment prevented UV-induced overexpression of IL-1 beta, IL-6 and COX2 mRNAs. Our data strongly suggest that PPs predominantly affect delayed molecular and cellular events initiated in NHEK by solar UV rather than primary photochemical reactions. PPs may be important component in cosmetic formulations for post-sun skin care.