Aim: The aim of this study was to investigate the effect of LPS in immune response through detecting some immune markers by IHC technique in the liver of mice infected with Leishmania donovani (VL). Methods: Three groups of eighteen mice were created: the first was control negative (non-infected), the second was control positive (infected with 2X107 promastigotes of Leishmania donovani), and the third group was infected with 2X107 promastigotes of Leishmania donovani and treated with 40 ng/ml of LPS. The treatment was given orally twice daily for one month. Mice were dissected, and the liver separated for an immunohistochemistry study for the markers (BCL-2, Caspase-3, CD3, CTLA-4). Results: The results showed there was significant elevation (p < 0.05) in the expression intensity (EI) for the markers in liver tissue of the control positive (infected) group compared with the control negative group and the group of mice infected with LV and treated with LPS; the EI (%) according to Aperio image program analysis were (0.90, 0.97, 0.93, 0.90) in the control positive, (0.82, 0.83, 0.85, 0.85) in the control negative, and (0.81, 0.89, 0.87,0.84) in the group of mice that were infected with LV and treated with LPS. Conclusion: The conclusion: 40 ng/ml of LPS had a role in providing protection to the liver from the effects of LV infection by modifying the innate and acquired immune response as a result of the decrease in the intensity of expression of BCL-2, Caspase-3, CD3 and CTLA-4, which also resulted from the occurrence of a reciprocal relationship between macrophages, hepatic parenchymal cells and non-parenchymal cells.