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BACKGROUND Despite Tricholoma matsutake has been used as natural health products with multiple medicinal properties, detailed information about its polyphenolic composition as sources of anti-photoaging agents remains to be determined. OBJECTIVE To investigate the impact of polyphenols extracted from Tricholoma matsutake (TME) on Ultraviolet B (UVB)-induced skin photoaging. MATERIALS AND METHODS Various factors of oxidative stress and inflammation as well as histological and immunohistochemical analysis in the mouse dorsal skin were determined after UVB radiation. RESULTS Topical administration with TME suppressed the UVB-induced skin thickness, wrinkles and erythema, and increased skin collagen content. Furthermore, TME decreased reactive oxygen species (ROS) level, upregulated glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and glucose-6-phosphate dehydrogenase (G6PDH) activities and inhibited the expression of IL-1, IL-6, IL-8 and TNF-α in mice irradiated with UVB. TME could reduce UVB-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-kappa B (NF-κB), thereby reducing the cyclooxygenase-2 (COX-2) expression, which is an important mediator of inflammatory cascade leading to the inflammatory response. CONCLUSION Our data demonstrated that TME had various beneficial effects on UVB-induced skin photoaging due to its antioxidant and anti-inflammatory activities, and it might be exploited as a promising natural product in skin care, anti-photoaging and the therapeutic intervention of skin disorders related to both oxidative stress and inflammation.