Toxoplasmosis is a widespread, neglected disease with significant morbidity and mortality. The cur-rent study aimed to investigate the potential effectiveness of azithromycin against the cystogenic Me 49 nonvirulent strain of Toxoplasma gondii after the 6th week post-infection (PI) in chronically infect-ed mice. Fifty laboratory-bred female Swiss albino mice were divided into five groups: G1: Non-Infected, G2: Infected non-treated, G3: Infected and treated by azithromycin 200 mg/kg after the 6th week PI for 3 days, G4: Infected and treated by azithromycin 200 mg/kg after the 6th week PI for 10 days and G5: Infected and treated by spiramycin 200 mg/kg after the 6th week PI for 2 weeks, brain cysts number, size and histopathological changes were evaluated after 2 months. The results showed that treating mice after the 6th week post-infection with azithromycin for 10 days reduced number and size of brain cysts by 64% & 30%, respectively, but without significant difference as compared with spiramycin-treated ones. Azithromycin treatment for 3 days achieved a greater re-duction (34%) in brain cyst size than the group treated with azithromycin for 10 days. But, it caused the least reduction in brain cyst number (10%). Azithromycin treatment for 10 days improved the his-topathological changes in cerebral toxoplasmosis.