Background: A chronic inflammatory illness with a relapsing remitting course is ulcerative colitis (UC). The primary test for UC diagnosis is a colonoscopy, however there is a chance that anything could go wrong. Inflammation of the mucosa has a lower correlation with UC indicators than colonoscopy. Interleukin 22 (IL 22), a member of the IL-10 family of cytokines, has only lately been linked to the pathogenesis of UC. Objective: The aim of this study was to evaluate the role of serum IL-22 as a novel non-invasive biomarker in diagnosis and assessment of activity in ulcerative colitis patients. Patients and Methods: This was a case control study that was conducted on 40 UC patients and 15 healthy controls at Ain Shams University Hospitals, throughout 6 months. Patients with ulcerative colitis were divided into 20 patients in clinical, laboratory and endoscopic remission and 20 patients in clinical, laboratory and endoscopic activity. Results: Statistical analysis revealed the following: For Interleukin 22, there was highly statistically significant difference found between the three groups. There was highly statistically significant correlation found between IL-22 (Pg/ml) and endoscopic activity, and there was statistically significant correlation found between IL-22 (Pg/ml) and Histological activity, and there was no statistically significant correlation found between IL-22 (Pg/ml) and Extent of the disease. IL 22 levels showed statistically significant correlations with erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and Mayo score of severity of UC. Receiver operating characteristic curve (ROC) showed that the best cut off point of IL-22 (Pg/ml) to detect Patients was found > 4.7 with sensitivity of 90.0%, specificity of 100%, PPV of 100.0%, NPV of 78.9% and total accuracy of 0.95%. (ROC) shows that the best cut off point of IL-22 to detect patients with activity was found > 10.2 pg/ml with sensitivity of 95.0%, specificity of 75.0%. Conclusion: It is concluded that IL22 is an important marker of ulcerative colitis activity as it shows significant correlation with endoscopic and histological activity.