Toxoplasmosis is a zoonotic parasitic diseasewith worldwide distribution. Chitosan is a natural polymerwhich is commonly used in the production of nanomedicines.It is known to enable higher drug permeation, beingbiocompatible and has very low toxicity, besides itsantimicrobial effects. Our study aimed to assess the effectof Spiramycin-loaded chitosan nanoparticles (SLCNs) intreatment of acute and chronic toxoplasmosis in mice. 200male Swiss albino mice were included in our study, dividedto two main groups; Toxoplasma gondii RH strain infectedgroup and ME49 strain infected group, each main groupwas subdivided into four subgroups; subgroup I: infectedcontrol, subgroup II: infected and received chitosannanoparticles (CS NPs); 20 lg of CS NPs in 100 ll ofPBS/mouse/dose, subgroup III: infected and treated withSpiramycin (Rovamycin); 100 mg/kg/day, subgroup IV:infected and treated with 100 mg/kg/day Spiramycin-loadedchitosan nanoparticles. Effect of treatment was assessedparasitologically and histopathologically. It wasnoticed that SLCNs significantly decreased the mortalityrate of infected mice with both strains compared to highmortality rate of mice in the infected control subgroups.Moreover, there was a significant decrease in the number oforganisms of SLCNs treated subgroup as compared to theother subgroups. Histopathological studies showed amarked improvement of the pathological pictures of brain,liver, spleen and eye in the subgroup received SLCNs asopposed to other groups. In conclusion, the present studyrevealed that loading of Spiramycin on chitosan nanoparticlesincreased its antiparasitic effect on acute and chronicT. gondii infection. Keywords: Toxoplasmosis - Spiramycin - Nanoparticles - Treatment – Histopathology