Toxoplasma gondii is an opportunistic protozoan that causes a devastating disease in immuno- compromised individuals and congenitally infected neonates or children. This study evaluated the efficacy of early Azithromycin treatment of Toxoplasma gondii infected mice with cystogenic Me 49 non-virulent strain. Fifty laboratory-bred female Swiss albino mice were divided into 5 groups: G1: Non-Infected, G2: Infected non-treated, G3: Infected and treated by Azithromycin 200 mg/kg at 4th day post-infection for 3 days, G4: Infected and treated by Azithromycin 200mg/kg at 4th day post-infection for 10 days & G5: Infected and treated by Spiramycin 200mgkg at 4th day post-infection for 2 weeks, brain cysts’ number, size and histopaholoical changes were assessed after 3 months. Treatment with Azithromycin for 10 days decreased number and size of brain cysts by 70% & 40% respectively without significant difference with Spiramycin treated mice that caused reduction by 74% & 50% respectively. Azithromycin treatment for 3 days caused the least reduction by 51% & 21% respectively and Azithromycin treatment for 10 days decreased the histo-pathological changes in cerebral toxoplasmosis. Azithromycin treatment started at 4th day post-infection was effective than Spiramycin against T. gondii infection with a significant effect on cysts count and size and brain pathological changes. Azithromycin treatment for 10 days gave better effect than 3 days