The peripheral HPA axis elements play important roles in the maintaining of skin local homeostasis. Inflammatory stimulation of AD may also activivate the skin HPA axis elements; the expression sequence of peptides includes urocortin/CRH!POMC!ACTH. However, unlike the central HPA axis, the elements of peripheral HPA axis have more close connections between each other and more complicated functions. Peripheral CRH is an important proinflammatory cytokine required for induction of the inflammatory response in vivo because acute stress response leads to increased skin vascular permeability and inflammation, largely through mast cell activation by CRH. The most potent anti-inflammatory treatments available for AD is glucocorticoid-based therapy, however, the prolonged use of glucocorticoids can cause various side effects, GANT61 therefore, it is imperative to explore other therapeutics which could increase the production or sensitivity of Dabrafenib abmole bioscience endogenous corticosteroid. Previously, we found that Shen-reinforcing and Qi-supplementing herbs could improve the symptoms of asthma rats and displayed anti-inflammatory effects via enhancing the expression of HPA axis. We also found that the main components of these herbs could attenuate LPS-induced inflammatory responses via inactivating NF-kB in vivo and in vitro, reverse social defeat-induced down-regulation of glucocorticoid receptor and promote adrenal gland weight gain, significantly restore plasma corticosterone and ACTH level. Therefore, we hypothesized that Shen-reinforcing and Qi-supplementing herbs might alleviate the symptoms of AD via improving central and skin HPA axis function, in addition to the anti-inflammatory and immunomodulatory effects. BuShenYiQi granule composed of two Shen-reinforcing herbs and one Qi-supplementing herbs, Herba Epimedii, Astragalus membranaceus and Rehmannia Root, in a ratio of 4:6:3, is often used to treat inflammatory diseases in Chinese Medicine. Despite its frequently clinical use and efficacy, the molecular mechanism of this therapy is not fully understood. In this study, we evaluated the anti-inflammatory effect of BSYQ in AD mice and explore the effective mechanism from regulation of HPA axis. We found 16 main components in BSYQ which were Icariin, Epimedin A, B, C, Baohuoside- I and Astragaloside IV etc. Our previous studies reported that these constituents could improve HPA function, and displayed anti-inflammatory, immunomodulatory, and antidepressant effects. This study showed that BSYQ treatment significantly alleviated abnormal symptoms and pathological changes in lesions of AD mice and presented anti-inflammatory and anti-allergic potential by systemically elevated levels of endogenous glucocorticoids and locally normalized function of skin HPA axis-like system.