Introduction: Psoriasis is a complex, common, chronic, non-contagious. The etiology of psoriasis remains poorly understood, but it is thought to be a complex of genetics, skin disruption, environmental, and immune dysfunction. Methods: This study extended from December 2020 to July 2021. Plant extraction was done at Baghdad Collage of Pharmacy (a private College) while animal experiments were done at College of Pharmacy, Baghdad University. The study involved 60 apparently healthy BALB/c male mice, which were divided into 6 groups where each group contained ten animals. Results: Psoriasis was induced on back skin of mice by the application of imiquimod cream, revealing significant histological and morphological changes in the skin in addition to the elevated levels of skin homogenate TNF-α, IL-17, IL-23 and VEGF, and elevated levels of circulated TNF-α, IL-17, and IL-23. Additionally, there was an increase in spleen index. The current study showed that using Artemisia annua extract ointment as prophylactic resulted in lower levels of inflammation, spleen index, skin homogenate TNF-α, IL- 17, IL- 23 and VEGF as well as lower levels of circulating TNF-α, IL- 17, and IL- 23. Conclusion: Both Artemisia annua extract ointment and Clobetasol showed an improvement in induced psoriasis, by decreasing the histological changes in skin, lowering cytokines level and in decreasing spleen index.