BACKGROUND The plant Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) is one of the members of the dashamula (ten roots) in Ayurvedic system of medicine. The stem and fruits are used as an antipyretic, antiasthmatic and is prescribed in skin infections and for relief in burning sensation in the feet accompanied by vesicular eruptions. OBJECTIVE To scientifically validate the anti-psoriatic potential of Solanum xanthocarpum stem in Imiquimod-induced psoriatic mice model. METHODS Ethanolic stems extract of Solanum xanthocarpum (ESX) was first subjected to phytochemical screening and quantification of identified phytoconstituents, which was further standardized with the help of HPTLC using chlorogenic acid as a marker. The extract was then subjected to acute oral toxicity and skin irritability study for determining the safety profile of the extract. Imiquimod-induced psoriatic mouse model was then performed to check the efficacy of extract against psoriasis, where treatment was carried out for 15 days both topically (Gel at 2.5%, 5% and 10%) as well as orally (at 100, 200 and 400mg/kg p.o.) and their Psoriasis Area Severity Index (PASI) was calculated. The study also included determination of levels of TNF-α, IL-1β, IL-6 and IL-17 in the animal tissues, which further included biochemical evaluations such as total collagen, hexosamine, hyaluronic acid DNA, protein antioxidant profiles such as lipid peroxidation, nitric oxide, superoxide dismutase and catalase along with histopathological studies of the tissues. RESULTS ESX showed the presence of mainly phenols, tannins, flavonoids, alkaloids and carbohydrates, while chlorogenic acid was reported to be 3.49% w/w. The Imiquimod-induced psoriatic mouse model, depicted a potent anti-psoriatic activity of the extract both topical (10%) and oral (200 and 400mg/kg p.o., as evident through PASI grading The effect was found to be more prominent in case of topically treated as compared to orally treated mice. The results also showed a significant inhibition in the expression of TNF-α, IL-1β, IL-6 and IL-17 in treated animal tissues and also showed significant restoration of the altered biochemical parameters along with reduced hyperkeratinisation as observed through histopathology. CONCLUSIONS The study scientifically justified the anti-psoriatic activity of the ESX, which may be attributed to inhibition in the expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-17. Further, the observed antioxidant, antimicrobial and cellular proliferative activities may act as a contributing factor in treatment of psoriasis, which may be attributed to the presence of chlorogenic acid along with other phytochemicals in combination.