Background: ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease that causes inflammation and ulcers in the innermost layers of the large intestine (colon) and rectum. Assessment of intestinal inflammation in UC is crucial and still remains a difficult challenge for the clinician. Although endoscopic modalities with biopsy sampling seem to be the most reliable method for estimating disease severity, they are invasive and costly. Apart from endoscopic interventions, disease severity can be assessed using both laboratory studies and non-invasive imaging tests. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBCs), acid glycoprotein, platelet count and albumin are in common use but have only modest accuracy in reflecting UC disease activity. Therefore, adjunctive use of additional serum markers that will be more sensitive and specific for determination of disease activity and achieving diagnostic accuracy is strongly needed in daily clinical practice. Aim of the Work: to investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of ulcerative colitis disease. Patients and Methods: a case control study that was conducted at the Gastroenterology Clinic, Internal Medicine Department, Ain Shams University during the period of January to July 2018. 60 patients were recruited for the study. They were divided as follows; Group “A": 40 patients newly diagnosed as ulcerative colitis based on colonoscopy and biopsy, subdivided as follows; 20 patients with active ulcerative colitis and 20 patients with inactive ulcerative colitis. Group “B": 20 healthy individuals free from any systemic diseases serving as a control group. Results: in this study, the serum levels of serum B2-microglobulins were highest in patients with active ulcerative colitis compared to those with inactive ulcerative colitis and the control groups. Also B2-microglobulins values become higher with higher number of presenting symptoms and endoscopic activity, which becomes higher in severe disease. Conclusion: our results revealed that serum B2-microglobulin was simple and non-invasive marker that could be helpful for differentiating active UC from inactive disease. Moreover, it was more helpful when used together with serum laboratory inflammatory indices (ESR and CRP).