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Introduction: Mammalian liver has highly regenerative capacity following resection or injury by restoring its original mass. However, in the endstage liver disorders, regeneration usually fails and orthotropic liver transplantation (OLT) seems to be the only curative approach. Cellular therapy is a promising approach that may preclude the need for OLT. Adult or embryonic hepatocytes and mesenchymal stem cells (MSCs) can be used for this purpose. Among them, MSCs are extrahepatic stem cells derived from bone marrow, adipose tissue, pancreatic epithelial progenitor cells, neural and umbilical cord blood-derived somatic stem cells have been shown to possess the potential to trans-differentiate into hepatic cells. Aim: To show the comparative, regenerative and curative effect of bone marrow MSCs on rats having hepatic fibrosis produced by common bile duct ligation (CBDL) model. Methods: Rats were divided into three groups; 1- CBDL rats that were given MSCs (CBDL+MSC), 2- CBDL rats that were given phosphate-buffered saline (PBS) (CBDL+PBS), 3- Healthy rats that were sham operated and given MSCs (Healthy+MSCs). Effect of MSC treatment were measured at three levels: morphological, phenotypical and functional. We analyzed the in vivo functional. Morphologically, MSCs were labeled with GFP to check the localization of stem cells and to get an idea for the regenerative capacity in the injured liver. Phenotypically, immunological studies were carried out to highlight the immune-regulatory effect of stem cells as to prevent apoptosis of hepatocytes, effects on the levels of regulatory T cells and pro-inflammatory T helper subsets such as Th1. Cytokine secretions from anti-CD2, anti- CD3 and anti-CD28 stimulated splenocytes (lymphocyte subtypes in spleen) were evaluated. Results: Histologically, liver fibrosis developed in CBDL rats while the entire group of healthy rats did not show any alteration in liver architecture. MSCs suppressed the rat splenocyte proliferation significantly more in CBDL+MSC compared with CBDL+PBS group (p<0,05). NK cells in peripheral blood increased significantly more in CBDL+MSC compared with CBDL+PBS (p<0.05). Peripheral CD4+ CD25+ ratio increased in CBDL+PBS compared with CBDL+MSC. MSCs suppressed the proinflammatory cytokine levels in CBDL+MSC. Discussion: Our findings suggest bone marrow derived MSCs may be effective in alleviating the hepatic injury by suppressing the spelonocyte proliferation, increasing the circulating peripheral NK cell population and CD4+CD25+ cells and by suppressing the proinflammatory cytokines in rats. Thus, MSC injection treatment may appear promising in liver injury and future clinical therapies are warranted. [ABSTRACT FROM AUTHOR]