Background: Psoriasis vulgaris (PV) has been considered as a frequent immune-mediated chronic, inflammatory dermal disease representing approximately 2% globally. Interleukin-22 (IL-22) is a recently described IL-10 family cytokine produced by a lot of cellular sources, which include Th17 and Th22 cells, and it plays an essential role in several autoimmune diseases (AIDs) such as rheumatoid arthritis (RA), and PV. Objective: To determine the diagnostic value of serum IL-22 level for PV; and to examine the possible correlation between serum IL-22 and disease severity and activity. Patients and Methods: This was a case control study conducted on 60 patients complaining from psoriasis; 30 patients complaining from active psoriasis, 30 patients with stable psoriasis, and 30 age- and sex-matched healthy controls (HC). Psoriasis area and severity index was used to assess both involved body area and clinical appearance of psoriatic lesions. Results: IL-22 was significantly increased among cases with active than stable disease and among progressive disease than intermittent disease. There was a statistically significant higher IL-22 among patients compared to HC. Area under curve (AUC) of IL-22 in differentiating patients from HC was excellent with sensitivity of 93.3%, specificity of 83.3% and accuracy of 90%. Conclusion: Interlukin-22 (IL-22) produces inflammatory signals which induce dermal and systemic manifestations in PV. IL-22 serum concentration may be an accurate marker of detecting severity of disease progression.