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Objective To investigate the clinical effects of bone marrow mesenchymal stem cell ( BMSC) transplantation via different approaches in the treatment of liver cirrhosis in mice. Methods A total of 46 BALB/c mice were randomly divided into normal control group with 5 mice and liver cirrhosis model group with 41 mice. Subcutaneously injected carbon tetrachloride olive oil was used to establish the mouse model of liver cirrhosis. A total of 36 mice with liver cirrhosis were randomly divided into control group, caudal vein BMSC transplantation group, and spleen BMSC trailsplantation group, with 12 mice in each group. Whole bone marrow adherent culture was performed to obtain the third - generation BMSCs, and flow cytometry was used for cell surface identification. BMSCs were injected into the mice through the caudal vein or spleen. Blood samples were collected at 4 weeks after transplantation to measure liver function. HE and Masson staining and a - smooth muscle actin (a -SMA) immunohistochemistry were performed for liver sections. Liver injury and fibrosis in mice were examined. A one - way analysis of variance was used for comparison between groups. Results At 8 weeks after the establishment of the model, the mice in the model group had sparse and dark yellow hair, reduced food consumption and activity, and a reduction in body weight. After transplantation, compared with the model control group, the caudal vein BMSC transplantation group and spleen BMSC transplantation group showed a significant increase in albumin and significant reductions in alanine aminotransferase and aspartate aminotransferase (all P < 0.01 ). There were no significant differences between the two transplantation approaches (P >0. 05 ). After transplantation, there were significant changes in diseased tissue, alleviated liver cirrhosis, reduced collagen fiber and necrotic area, and a good structure. Immunohistochemistry showed both transplantation groups showed significant reductions in the number of cells with positive a - SMA. Conclusion BMSC transplantation via the tail vein or spleen can improve liver function and diseased tissue in mice with liver cirrhosis and these two approaches have comparable clinical effects. [ABSTRACT FROM AUTHOR]