Background: Mesenchymal stem cells (MSCs) have the ability to improve inflammatory diseases through its anti-inflammatory effect as well as tissue regeneration via cellular differentiation. Additionally curcumin plays an important curative role in colonic injury through its anti-inflammatory, antioxidant and anti-fibrotic effect.Aim: this work was done with the aim of evaluating and comparing the possible therapeutic regenerative effect of both bone marrow derived MSCs and curcumin on experimentally induced animal model for chemical colitis in male albino rats. Material and methods: the present work was carried out on 42 adult male albino rats, divided into 4 groups. Group I (control) included 12 rats, group II (colitis):10 rats that were received once intra-rectal injection of 2 ml of 3% acetic acid. Group III (curcumin): 10 rats that were received daily oral curcumin through gastric tube at a dose of (100 mg/kg b.wt.). Curcumin started 24 hours after the induction of colitis and continued until the time of scarification. Group IV (MSCs): 10 rats that were received a single injection via tail vein of 5×105 MSCs/150μl in Dulbecco’s phosphate buffered saline 24 hours after colitis induction. In each of experimental groups (II, III and IV), the rats were subdivided into subgroups (a&b). (Subgroup a) corresponds to the rats that were sacrificed at 3 days after induction of colitis. (Subgroup b) corresponds to the rats that were sacrificed at 10 days after induction of colitis. Specimens of the distal 3cm of the colon were excised, processed and stained with hematoxylin and eosin, alcian blue, masson's trichrome, immunohistochemichal stain for alpha smooth muscle actin (α-SMA) and PKH26 immunofluorescence stain. The area percent of mucin, optical density of mucin, area percent of collagen fibers, number and optical density of α-SMA immunoreactive myofibroblasts were measured in all experimental groups and statistically analyzed.Results: In colitis group, ulceration, lymphatic nodule piercing the muscularis mucosa, disturbed crypts architecture and reduction in goblet cells were reported. In curcumin and stem therapy groups at 3 days, few signs of tissue regeneration were recorded in the form of partially intact surface epithelium with adjacent area of stratification. However, at 10 days of therapy, apparently intact mucosal lining and crypts with increased goblet cells were observed. The crypts were slightly spaced by little inflammatory cell infiltration. Regarding the morphometric results, there was more statistical significant signs of regeneration of MSCs treated rats than that treated with curcumin.Conclusions: Either curcumin or MSCs represent new methods in treatment of colitis due to their effective role in colonic repair and dampen the inflammation with more pronounced regenerative effect of MSCs than curcumin on colonic injury.