Visceral leishmaniasis consider a great health problem in Iraq, the traditional antileishmanial therapies are toxic and most are costly. For this reason, new approaches in the treatment of leishmaniasis are requested, zirconia nanoparticles ZrO2NPs, is a nano-sized and hollow colloidal metal oxide, it was recorded as anticancer agent, the approach was to prepare 17.4 μg/ml of ZrO2NPs by pulsed laser ablation. These nanoparticles are described to confirm the shape, size and other physical properties of the crystal using the following techniques: X-Ray Diffraction (XRD), results were indicated diffraction peaks at (28.2°, 31.5°, 38.5°, 50°, and 59.8°) were correspond to the (111, 111, 120,022 and 131), respectively. The Transmission Electron Microscopy (TEM) shown confirms the formation of nanostructures with granular size by 50 pulses of laser. The histological study included preparation of cross-sections of liver tissue of infected mice and dosed with ZrO2NPs, the results exhibited mild central venous congestion and mild sinusoidal dilation after 7th day of administration and normal appearance with a few infiltration of hepatocytes and small necrosis, hydropic degeneration after 21th day compared with control positive group which exhibited moderate central venous congestion, mild infiltration and the magnified sections revealed moderate cellular swelling and necrosis of hepatocytes after 7th day and became sever damage with multiple focal necrosis, sinusoidal dilation, and infiltration of inflammatory cells with disarrangement of hepatic cords and increased kupffer cell after 21th.