Ulcerative colitis is common and complex conditions that are difficult to cure. MiRNAs are a class of small, non-coding, single-stranded RNA molecules which play a key role in autoimmune and inflammatory diseases especially in IBD. Despite the efficacy of biological treatment, a significant proportion of patients with IBD do not show an adequate response. For this reason it is crucial to identify biomarkers useful to predict clinical response. In present study, we aimed to evaluate the microRNA-155 (miR-155) and microRNA-223 (miR-223) as prognostic marker in disease response to therapy in patients with UC. This study included 80 patients with UC (40 patients who response to conventional treatment and 40 who resist and they are on biological treatment) and 40 healthy controls. Real-time polymerase chain reaction (RT-PCR) assay was performed for evaluation miRNA-155 and miRNA-223. According to the results of this study, There was significant variation in mean fold change of miR-155 among groups (p 4.51with 25 % sensitivity level, 92.5% specificity level and 59.1 % accuracy level. In conclusion, this study have evaluated the therapeutic response to corticosteroid, or IFX therapy and blood expression of miRNA by screening the responses to anti-TNF-α and conventional therapy, this study demonstrated that the level of miRNA-223 associated with the response to IFX which is highly increased in biological therapy (negative response) comparing to the conventional therapy (positive response) group after IFX therapy while the present study demonstrated that miRNA-155 fold change upregulated in patients with ulcerative colitis and on conventional therapy (positive response) in comparison with healthy control group.