The present investigation was conducted to study the effect of infection with Toxoplasma gondii and the efficacy of azithromycin and garlic tablets on treatment of acute murine toxoplasmosis in addition to study the histopathological changes due to infection. For this purpose, sixty Albino mice were used as experimental animals that equally divided into 6 groups. Estimation of survival rate, pathological studies, bioassay trial and immunofluorescent study were performed for each group of mice. High efficacy of azithromycin at a dose of 250 mg/kg/day on infected mice was shown, that increased survival rate (90% at the 7^th day P.I) and decreased the histopathological changes when compared with control groups. Garlic tablets at a dose of 500 mg/kg/day showed fewer efficacies in infected mice, survival rate (40% at the 6^th and 7^th day P.I) which was lesser than those groups treated with azithromycin. Pathologically, group treated with azithromycin showed improvement in histological pictures compared with group treated with garlic. To identify the efficacy of the drug, at the end of the experiment, subinoculation of healthy mice by visceral and brain suspensions from surviving mice treated with azithromycin or garlic was performed as compared with subinoculation of suspension of brain and visceral of infected non treated mice inoculated into healthy mice, that showed death of these mice after three days post-infection (survival rate 0 %). It was concluded that azithromycin has a significant effect in treatment of murine model toxoplasmosis, but it did not eradicate the parasite completely as few cysts remained in the brain, while garlic tablets had a limited effect for treating toxoplasmosis.