Objective  Ulcerative colitis usually affects the rectum and potentially can involve the whole colon. Noninvasive methods such as fecal calprotectin measurement may be considered as a reliable and inexpensive approach in assessing disease severity or treatment change strategy. Methods  In this retrospective cross-sectional study, records of 56 ulcerative colitis patients who hospitalized with exacerbation between May 2016 and April 2017 were assessed based on IBD Data Bank Software in Gastrointestinal and Liver Diseases and Research Center (GLDRC), Guilan province, Iran between. A questionnaire of demographic characteristics, clinical findings and fecal calprotectin level was completed. Montreal classification severity of ulcerative colitis and Mayo disease activity index were scored. Data were analyzed for descriptive and analytical analysis. Results  Fecal calprotectin was significantly different in terms of disease severity based on both Mayo score ( p = 0.007) and Montreal classification ( p = 0.001). In patients with mild symptoms, no increase in fecal calprotectin was observed, but in patients with moderate and severe elevations in fecal calprotectin levels was significant. Also, C-Reactive Protein surge was related to disease severity ( p = 0.02). Furthermore, regression comparison among high-chance patients based on fecal calprotectin was significantly related to higher Erythrocyte Sedimentation Rate levels and smoking, p = 0.01 and p = 0.05, respectively. Conclusion  It seems fecal calprotectin levels are related to the disease severity. Non-invasive methods, such as fecal calprotectin assay, may seem to be an alternative to aggressive, costly and time-consuming methods, such as colonoscopy and biopsy, to reduce the suffering of patients and ultimately help improve the patients’ life quality.