Objective: This study aimed to explore the improvement effect of sesamol on skin lesions caused by psoriasis. Methods: The psoriasis model was constructed by using 5% imiquimod cream applied to the backs of mice for seven consecutive days, with sesamol intervention used from one week before to the end of modelling to explore the protective effect of sesamol on the skin. Then, observed and measured skin thickness, PASI score, spleen index, pathological tissue sections, cytokines (IL-17, IL-23, TNF-α and other inflammatory factors and chemokines like CXCL1 and CCL20), and inflammatory factors (IL-17, TNF-α) in plasma of mice in each group, to analyze the effect of sesamol on the inhibition of psoriasis-like inflammation in mice. Results: The results showed that the skin of the model group of mice showed typical lesion manifestations and pathological features of psoriasis on the back. The application of 3% sesamol solution inhibted skin lesions and epidermal hyperplasia, decreased splenic index, and significantly reduced the expression of cytokines in skin tissues and plasma. Conclusion: Sesamol can significantly ihhibit the skin lesions, reduce the pathological features, and down-regulate the expression of inflammation of mice in psoriasis model.