【Abstract】 Objective The aim of this study was to explore the mechanism of GS-9620 in improving imiquimod (IMQ) -induced psoriasis-like inflammation by regulating Th1/ Th17-related immune response, and to further investigate its regulatory effect on gut microbiota in mice. Methods The IMQ-induced psoriasis-like inflammation model was established in BALB/c mice. PASI score was used to evaluate the severity of skin lesions. Flow cytometry was used to detect the proportions of CD4+IL-17+ and CD4+IFN-γ+ cells in spleen tissue. The levels of inflammatory factors such as TNF-α, IL-1β and IL-6 in skin tissues were determined by ELISA, and pathological analysis was performed by H E staining. 16S rRNA sequencing was performed on the gut microbiota of mice in the control group, IMQ model group and GS-9620 treatment group to analyze the effect of GS-9620 on the gut microbiota structure. Results GS-9620 significantly reduced the PASI score of IMQ-induced mice, and effectively inhibited the proportion of CD4+IL-17+ and CD4+IFN-γ+ cells in the spleen. At the same time, GS-9620 significantly down-regulated the expression levels of TNF-α, IL-1β and IL-6 in skin tissue. 16S rRNA sequencing analysis showed that GS-9620 can significantly regulate the abundance of gut microbiota related to inflammation, including the relative abundance of bacteria such as Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-008, Alloprevotella, Desulfovibrio, Prevotellaceae_UCG-001 and Alistipes. Conclusions By regulating the expression of Th1/Th17 related inflammatory factors, GS-9620 effectively alleviates IMQ-induced psoriasis-like skin inflammation in mice. In addition, it may improve IMQ-induced clinical symptoms by regulating the gut microbiota structure, which provides a new theoretical basis for the treatment of psoriasis through microbiota regulation. The results of this study provide an important experimental evidence for further exploring the application value of GS-9620 in psoriasis treatment.