||Photoaging is the clinical manifestation of chronic damage in skin tissue induced by solar light irradiation, which is one of the most common challenges for skin tissue. Solar light irradiation can increase oxidative stress by inducing reactive oxygen species (ROS) generation. Increased ROS generation leads to oxidative damage in biomolecules, with resultant adverse biological consequences in skin tissue such as premature senescence of cell and degradation of extracellular matrix by matrix metalloproteinases (MMPs). As such, the photoaging of skin is manifested by coarse and leathery wrinkle, and reduced skin resilience. Since photoaging is mediated through solar light irradiation-induced ROS generation, the use of antioxidants that can scavenge ROS represents a rational strategy for the prevention of photoaging aging. Schisandrin B (Sch B), which is the most abundant active ingredient in the fruit of Schisandra chinensis, was found to produce tissue non-specific antioxidative effect by enhancing cellular and mitochondrial glutathione antioxidant status in the heart, liver and brain of rodents. Therefore, the administration of Sch B on skin tissue may be effective in preventing the photoaging of skin. In present study, it was found that topical application of Sch B on rat skin could enhance glutathione antioxidant status, as well as prevent oxidative damage of rat skin tissue in control and solar light-irradiated condition. By using BJ human skin fibroblasts, it was demonstrated that Sch B treatment could protect human skin fibroblasts against solar light irradiation, and decrease MMP-1 expression and elastases-type protease activity. To explore the biochemical mechanism underlying the Sch B-induced glutathione antioxidant response in skin tissue, cytochrome P-450 (CYP)-catalyzed reaction with Sch B or its analogs and the associated ROS production were examined in rat skin microsomes and human skin fibroblasts. Sch B and schisandrin C, which could enhance glutathione antioxidant status in both skin tissue and BJ human skin fibroblasts, were found to induce NADPH oxidation and ROS production in rat skin microsomes, as well as a CYP-dependent ROS production in BJ human skin fibroblasts.