BACKGROUND Primary biliary cholangitis (PBC) is a chronic autoimmune-mediated cholestatic liver disease. Nanoparticles encapsulating rapamycin (ImmTOR) suppress adaptive immune responses and induce the hepatic tolerogenic immune response. AIM To investigate the effects of ImmTOR in PBC mouse models. METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals, and polycytidylic acid every three days. The PBC mouse models were separated into the treatment group and the control group. The levels of alkaline phosphatase (ALP) and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer. Liver and spleen mononuclear cells were analyzed by flow cytometry, and serum anti-mitochondrial antibodies (AMA) and the related cytokines were analyzed by enzyme-linked immunosorbent assay. Liver histopathology was examined by hematoxylin and eosin staining and scored. RESULTS After treatment with ImmTOR, the ALP level was significantly decreased (189.60 U/L +/- 27.25 U/L vs 156.00 U/L +/- 17.21 U/L, P < 0.05), the level of AMA was reduced (1.28 ng/mL +/- 0.27 ng/mL vs 0.56 ng/mL +/- 0.07 ng/mL, P < 0.001) and the expression levels of interferon gamma and tumor necrosis factor alpha were significantly decreased (48.29 pg/mL +/- 10.84 pg/mL vs 25.01 pg/mL +/- 1.49 pg/mL, P < 0.0001) and (84.24 pg/mL +/- 23.47 pg/mL vs 40.66 pg/mL +/- 14.65 pg/mL, P < 0.001). The CD4+ T lymphocytes, CD8+ T lymphocytes and B lymphocytes in the liver were significantly reduced, with statistically significant differences (24.21% +/- 6.55% vs 15.98% +/- 3.03%, P < 0.05; 9.09% +/- 1.91% vs 5.49% +/- 1.00%, P < 0.001; 80.51% +/- 2.96% vs 75.31% +/- 4.34%, P < 0.05). The expression of CD8+ T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased (9.09% +/- 1.91% vs 5.49% +/- 1.00%, P < 0.001; 80.51% +/- 2.96% vs 75.31% +/- 4.34%, P < 0.05). The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score, and the difference in the scores was statistically significant (4.50 +/- 2.88 vs 1.75 +/- 1.28, P < 0.05). CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+ T cells and B cells, and reducing the titer of AMA.