Objective: The objective of this study was to compare between the efficacies of mesenchymal stem cell (MSC) and betamethasone in the treatment of rheumatoid arthritis.Material and method: 90 male albino mice were divided equally into 2 models as follows: MSC model, group 1: saline control group, group 2: Acetic acid, group 3: CIA, group 4: induced arthritis mice that received intravenous injection of MSCs. Betamethasone model, group 1: phosphate buffer saline, group 2: Acetic acid, group 3: betamethasone control, group 4: CIA, group 5: induced arthritis mice that received intraperitoneal injection of betamethasone. Mice arthritis models were assessed by clinical paw edema and x-rays, at the proper time of sacrefaction, tissues were collected and examined using real-time PCR (RT-PCR), synovial tissue was examined for (IL-10) interleukin-10 (TNF-α), tumor necrosis factor-α, (COMP)-Cartilage oligomeric matrix protein, (MMP-3) Matrix metalloproteinase3. While (MDA), (LDH), (GSH), (CAT) and (MPO) were determined using colorimetric kits. In addition detection of serum level of (IgG), (RF), (CRP), (ANA) by enzyme-linked immunosorbent assay (ELISA).Also detection of blood (ESR).Results: Histopathological, paw edema and PCR results showed improvement of the group that received MSC compared to the diseased group and group received betamethasone. Conclusion:MSC significantly enhance the efficacy of collagen-induced arthritis treatment, which is superior to betamethasone treatment likely through the modulation of the expression of various cytokines.