Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is an inflammatory condition that results in gastrointestinal tract damage. Various factors, including environmental and genetic agents, disrupt the function of the intestinal immune system that can lead to IBD. Mesenchymal stem cells (MSCs) display an immunoregulatory function and demonstrate regenerative potential by paracrine action. In this study, we evaluated the immunomodulatory effects of MSCs’ derived exosomes in the acute form of dextran sulfate sodium (DSS)‐induced colitis. Exosomes were isolated from adipose‐derived MSCs. Acute colitis was induced by DSS. The exosome was used by intraperitoneal injection into mice with acute colitis. Stool consistency, body weight changes, bleeding severity, colon length, and weight were examined. At the experimental endpoint (Day 7), the changes in the colon tissue were evaluated. The level of cytokines of interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), interleukin‐17 (IL‐17), IL‐4, IL‐12, transforming growth factor‐β (TGF‐β) and, IL‐10, and Treg cells percentage were assayed. Results showed that exosome administration diminished colon shortening, bodyweight loss, bleeding, and colon injury. The levels of IFN‐γ, TNF‐α, IL‐12, and IL‐17 were decreased, and the level of TGF‐β, IL‐4, and IL‐10 were increased in lymph node and spleen of mice treated with exosome.  Percentages of CD4⁺ CD25⁺ Foxp3⁺ Treg cells were grown in the lymph node and spleen of mice treated with exosomes. Overall, current data suggest that MSC‐derived exosome could regulate the Treg population and improves inflammation in DSS‐induced acute colitis.