Background: Silver nanoparticles (AgNPs) can be used as vehicles to transport drug molecules to target zones and there by improve their therapeutical efficacy. Aim: The aim of the present work was to assess the effect of nitazoxanide loaded on silver nanoparticles (AgNps) in treatment of chronic toxoplasmosis in mice. Materials and methods: Mice were infected with T. gondii Me49 non-virulent strain and divided into 2 subgroups according to the time of starting treatment, and each subgroup sub divided into 7 groups. GI: Non infected- non- treated, GII: Infected non-treated mice, GIII: Infected and treated by spiramycin, GIV:  Infected and treated by nitazoxanide, GVa:Infected and treated by nitazoxanide loaded on silver nanoparticles, GVb:Infected and treated bynanosilver only, GVI:  infected and treated by combination of nitazoxanide and spiramycin, GVII:infected and treated by combination of nitazoxanide loaded on silver nanoparticles and spiramycin. Effect of treatment was assessed by counting the number of T. gondii brain cysts, histopathology and scanning electron microscopy. Results: Nitazoxanide loaded on AgNps significantly reduced the number of T. gondii brain tissue cysts and improved the inflammatory and pathological changes in brain tissue sections in treated groups as compared to the other groups. It also affects the normal architecture and size of tissue cysts in brain. Conclusion: Nitazoxanide loaded on AgNps proved their effectiveness against the experimental chronic Toxoplasma infection.