Antileishmanial role of mouse splenic natural killer (NK) cell was studied in allogeneic condition. In vitro data indicates that NK cells of allogeneic (C57BL/6, H2b) non-leishmania exposed mouse have strong antileishmanial effect against Leishmania donovani infected BALB/c (H2d) macrophages. Physical contact between the effector (NK cell) and the target cells (infected macrophages) is essential in this system since; cell free supernatant generated after coculturing of effector cells with infected target cells fails to elicit any antileishmanial effect. Although NK cells from allogeneic mouse are strongly attached to the infected macrophages but unable to kill it in such interaction. The antileishmanial effect of allogeneic NK cells is mediated by TNF-α and not by IFN-γ. In vivo cellular therapy of established infection with NK cells from non-leishmania exposed allogeneic mouse significantly reduces the total parasite burden in the spleen of infected animal.