Abstract There is a great need for compounds with antioxidant and anti-inflammatory properties for protection against UV radiation, which is the most prooxidative physical factor that skin cells are exposed to everyday. Therefore, the aim of the study was to evaluate the mechanism of phytocannabinoid-cannabidiol (CBD) action in vivo on lipid metabolism in keratinocytes of rat skin exposed to UVA/UVB radiation. Our results show that CBD protects keratinocytes against the effects of UVA/UVB radiation by reducing lipid peroxidation products: 4-HNE and 8-isoPGF2α. In addition, CBD significantly increases the level of endocannabinoids, such as anandamide, 2-arachidonylglycerol, and palmitoylethanolamide, and the activation of their receptors CB1/2...