Background: Schistosomiasis mansoni causes fibrosis that progress to cirrhosis and liver cell failure. Mesenchymal stem cells (MSCs) based therapy has promising effect in treatment of liver diseases. Objectives: Studying the therapeutic potential of stem cell injection on liver fibrosis in Schistosoma (S.) mansoni infected mice. Methods: A) Pilot study was carried out to ensure homing of MSCs in the fibrosed liver of S. mansoni infected mice. B) Experimental study: S. mansoni infected mice groups (untreated, PZQ treated, MSCs treated and PZQ+ MSCs treated) and non-infected control mice were studied to evaluate the effect of treatment regarding the parasitological parameters and by assessment of serum albumin level and liver enzyme, alanine tranferase (ALT). Stained liver sections by hematoxylin and eosin (H &E), Masson trichrome (MT) and immunohistochemical for transforming growth factor beta-1 (TGF-β1) were also examined. Results: Serum albumin level was significantly improved in PZQ and PZQ +MSCs treated groups. Serum ALT level was significantly reduced in PZQ and MSCs treated groups. High significant reduction in granuloma size was found in MSCs treated group and granuloma number significantly reduced in PZQ +MSCs treated group .TGF-β1 expression encountered significant reduction in PZQ treated group and non-significant reduction in other infected treated groups. Conclusion: Peripherally injected MSCs can migrate and settle in the injured liver of S. mansoni infected mice leading to significant reduction in granuloma size, ameliorate hepatic fibrosis and hepatic functions improvement.