Objective: To assess the effect potency, and the immunomodulatory response of garlic oil extract in enhancing the host's immune system against the disorders caused by Schistosoma mansoni ( S. mansoni) in mice at different stages of worm maturation. Methods: A total of 70 male CD-1 Swiss albino mice were divided into 7 groups. Group I: healthy control. Group II: garlic oil group orally administrating 100 mg garlic oil extract/kg b.wt. 3 d a week for 6 weeks. Group III: infected with S. mansoni cercariae and left untreated for 42 d. Group IV: treated with garlic oil extract from day 1 to day 7 post infection (PI). Group V: treated with garlic oil extract from day 14 till day 21 PI. Group VI: administrating garlic oil extract from day 35 until day 42 PI. Group VII received oil extract from the first day of infection for 42 d. Results: Garlic oil extract showed changes in the parasite tegument with a significant decrease in worm burden, hepatic and intestinal ova count with a decline in granuloma number and diameter. These alterations were accompanied with a reduction in serum TNF α, ICAM-1, IgG and IgM after 7 and 42 d post S. mansoni cercarial infection. Conclusions: Results obtained confirmed the effect of garlic oil extract on the larval and mature stage of the parasite and in enhancing the host's immune system against the disorders caused by S. mansoni in mice.