Background & Aim Background & Aim: A new subset of macrophages has been found to be involved in process of hepatic fibrosis, which is called Ly-6C. This group of macrophages shows differences in terms of cytokines compared to common macrophages classification. The most important feature of this group is the low expression of TGF-β cytokine in comparison with macrophage M2, which can be a positive factor in stopping the process of liver fibrosis. In the present study, the role of mesenchymal stem cells in the polarization of Ly-6C macrophages through the CX3CL1 pathway was investigated in the healing process of liver fibrosis. Methods, Results & Conclusion Methods: Sprague Dawley rats were used for inducing experimental model of liver fibrosis by using CCL4. The rats were divided into 3 groups including; mesenchymal stem cell recipient group, Fibrotic experimental group as well as healthy group. Serological, molecular, pathological tests, Western blotting, flow cytometry and IHC were used to evaluate the development and stopping of the disease. The expression levels of macrophage and chemokine markers were evaluated using Real-time PCR. Results Rats adjacent to CCL4 based on Metavir index showed mainly fibrosis with F3 and F4 degrees. Also, changes in ALT/AST, ALb and fibrotic markers including; procollagen I and III, as well as α-sma at the molecular and protein levels showed significant differences between healthy and fibrotic samples. In the mesenchymal stem cell-treated group, there was a significant decrease of extracellular matrix components α-sma and serum markers (p Conclusion In the present study, it has been shown that in the process of fibrosis amelioration, mesenchymal stem cells can play a role in polarization of macrophages from Ly-6C-high (inflammatory) to Ly-6C low (anti-inflammatory) by elevating the level of CX3CL1, which can have a significant impact on the improving of liver disease.