Background: Toxoplasmosis is a zoonotic disease caused by the intracellular opportunistic protozoan,T. gondii that infects both vertebrate and invertebrate cells. Nanoparticles (NPs) provide promisingtherapeutic agents for effective treatment of parasitic diseases, by overcoming the drawbacks of lowbioavailability and poor cellular permeability of anti-parasitic drugs.Objective: To assess the therapeutic effect of gold (Au) NPs on experimentally infected mice with chronictoxoplasmosis.Material and Methods: Sixty-five laboratory-bred female Swiss albino mice were included. Five micewere left as control negative (non-infected non-treated), while the rest were experimentally infectedorally with avirulent T. gondii strain (ME49). Fifty days post infection (pi), infected mice were dividedinto 4 groups (15 mice each); group 1: control group (infected non-treated); group 2: treated withSpiramycin (Rovamycin); group 3: treated with low-dose AuNPs; and group 4: treated with high-doseAuNPs. Treatment was administered orally for 10 days. All mice were sacrificed sixty days pi. Assessmentof the therapeutic effect of AuNPs was achieved using parasitological, histopathological and biochemicalparameters. The first included estimation of the parasite tissue cysts numbers and size in impressionsmears from brain, liver and spleen; histopathological parameters evaluated inflammation, necrosis andhemorrhages in tissues. Liver transaminases: aspartate transaminase (AST) and alanine transaminase(ALT) were measured in sera of all groups as a biochemical parameter.Results: Statistically significant reductions were observed in the mean cyst count and size in brain, liver,and spleen of the infected treated group with high dose AuNPs (group 4) compared to the other infectedgroups. Histopathological examination of the brain, liver and spleen tissues showed that inflammatoryreaction was decreased in both AuNPs-treated groups in comparison to Spiramycin-treated group and thenon-treated mice. There was a significant reduction in the mean values of ALT and AST in mice treatedwith AuNPs high dose in comparison to other groups (P<0.05).Conclusion: AuNPs have a potentially therapeutic effect especially the high dose against experimentalchronic toxoplasmosis.