Abstract: Objective: To study the expression and the clinical significance of CD28 on CD8⁺ T lymphocytes in liver tissue of hepatitis B patients.Methods: One hundred cases of hepatitis B patients were divided into mild,moderate and severe hepatitis B groups according to the pathological changes of liver tissues,and normal liver tissue of 15 healthy persons as the control group.CD8⁺CD28⁺ and CD8⁺CD28^-T lymphocytes were determined in liver tissue with immunohistochemical double-labeling.Results: The CD8⁺CD28⁺ and CD8⁺CD28^-T lymphocytes in hepatitis B patients were significantly higher than those in control group (P<0.05).In hepatitis B patients with mild lesions,CD8⁺CD28⁺ T lymphocytes were decreased significantly compared with control group,in hepatitis B patients with moderate and severe lesions,CD8⁺CD28⁺ cells and CD8⁺CD28^-T lymphocytes were increased significantly compared with control group (P<0.01).CD8⁺CD28⁺ T lymphocytes were raised with the liver inflammation grades,but CD8⁺CD28^-T lymphocytes were reduced gradually with the liver inflammation grades.Conclusions: The expression of CD28 on the surface of CD8⁺ T lymphocytes in liver tissue of patients with hepatitis B is closely related to liver tissue lesion.The CD8⁺CD28⁺ T lymphocytes in liver tissue can be used as immunological markers of liver injury in patients with hepatitis B.CD8⁺CD28^-T lymphocytes in liver tissue may be the main reason for persistent infection of hepatitis B virus.