Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)-induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin-draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin-draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor-beta (TGF beta) messenger RNA (mRNA) and interleukin-23 (IL-23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGF beta/PU.1/IL-23 signal axis. In this study, we explore the regulatory mechanism of Yinxieling (YXL), a clinically effective Chinese herbal medicine, on the differentiation and functions of langerhans cells (LCs) in psoriasis-like mice. As the results show, YXL significantly alleviates psoriasis-like skin inflammation induced by IMQ in mice. Although it has no obvious effect on dendritic cells in skin-draining lymph nodes, it can significantly reduce the expression of LCs and PU.1+LCs in skin lesions, as well as inhibits the migration and maturation of LCs, and prevent its antigen presentation so as to effectively alleviate the psoriasis-like skin inflammation on mice. Our investigation provides experimental basis to better understand the mechanism of traditional herbal medicine for psoriasis.