The influences of chronic UVB exposure on epidermal differentiation have been poorly studied compared to dermal photo-aging although those effects are very important in terms of photo-damage to the skin. The purpose of this study was to investigate the effects of chronic UVB exposure on keratin expression in the epidermis. The effects on murine skin of chronic exposure to weak UVB (below 1 MED) was examined by immunoblotting for keratins K10, K5, K6, and K16, by immunohistochemistry using antibodies to K6, K16, and Ki67 as well as by conventional HE staining of skin sections. Alterations of keratin expression induced by the chronic UVB exposure were distinct from those elicited by a single acute UVB exposure. The expression of keratins K6 and K16 was quite long-lasting, continuing for 7 weeks after 6 weeks of chronic UVB exposure and for 6 weeks after 9 weeks of chronic UVB exposure. In contrast, K6 and K16 expression induced by a single UVB exposure at 0.5 MED or 3 MED almost ceased within 2 weeks after that exposure. Furthermore, the expression of the constructive keratins, K5 and K10, remained almost unchanged by chronic UVB exposure. Epidermal thickness was increased significantly immediately after the 9 weeks of chronic UVB exposure; however, it had returned to normal level 6 weeks later. The alterations in keratin expression accompanied the marked disruption of the ordered ultrastructure of keratin intermediate filaments, which were observed by TEM. Thus, chronic exposure to UVB has a deep impact on the biosynthetic regulation of different keratins in the epidermis, thereby interfering with the ordered ultrastructure of keratin intermediate filaments. Those events could have relevance to the mechanism of photo-damage, such as fine wrinkles observed in chronically UV-exposed skin in addition to dermal photo-aging.