Background: Ulcerative colitis (UC) is a bowel inflammatory illness, which shows remission and deterioration episodes of abdominal pain and bloody diarrhea. Nowadays, treatment options are not satisfactory other than their various complications. Adipose tissue derived mesenchymal stem cell microvesicles (MSC-MVs) are considered an emerging promising alternative therapeutic agent. Aim of the work: Evaluation of the therapeutic potential of MSC-MVs on acetic acid (AA) induced UC in addition to the potential role of its RNA content. Materials and Methods: Forty adult male albino rats were equally divided to 4 groups: group I (control), group II (colitis), group III (MVs treated) and group IV (RNase-MVs treated). Colitis was induced by intracolonic AA enema for groups II, III and IV. On day three after enema a single intravenous injection with either PBS, MSC-MVs or RNase treated MSC-MVs was administered to groups II, III and IV, respectively. Seven days later, colon specimens were harvested and cut equally into two parts. The proximal parts were used for biochemical study to measure myeloperoxidase enzyme (MPO) levels. The distal parts were processed for H&E, Alcian blue, iNOS and COX-2 immunohistochemistry. Morphometric and statistical analysis were done. Results: Group III showed improved histological features of UC and marked increase in the mean area percent and optical density of mucin. Also, it showed significant decrease in iNOS and COX-2 immunoreaction and MPO levels. Conclusion: MSC-MVs administration improved UC features. RNA content of the vesicles proved to have a crucial role in such protective effects. Consequently, MSC-MVs could be a promising tool in UC treatment.