This work was carried out to investigate the effect of silymarin combination in the therapeutic plane of schistosomiasis with praziquantel or mirazid to enhance the liver and reduce fibrosis. Mice were divided into 2 main groups, the 1st uninfected group served as control and the 2nd group infected subcutaneously with 60 cercaria of S. mansoni per each. The infected group was subdivided into 5 subgroups, the 1st kept untreated, the 2nd and 3rd treated at the 7th week of infection with (600

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... ) of PZQ orally for 3 consecutive days, while the 3rd treated also orally with (150 mg/kg) of silymarin daily for 11 weeks. The 4th and 5th groups treated orally at the 7th week of infection with 600 mg/kg of MZ for 3 consecutive days, while the 5th group treated orally also with 150 mg/kg of silymarin daily for 11weeks. IgG determination showed high level in the untreated infected group. Furthermore, the infected groups treated with PZQ and PZQ with silymarin displayed the lower levels than treated with MZ. Additionally, the untreated infected group showed severe pathological changes as hyaline degeneration, inflammation, presence of worm burdens in dilated portal veins, granulomas as well as depositions of collagenous and reticular fibers indicated intense fibrosis. Treatment with PZQ alone resulted in reduction of pathological signs and decreasing of granulomas. Combination with silymarin to PZQ therapy revealed more improvement for liver besides to lowering of granulomas areas and volumes and decreasing of fibrosis. Whereas, treatment with MZ was less effective than PZQ to reduce granulomas areas, volumes and fibrosis. Although, combination of silymarin to MZ treatment resulted in more curative signs and reduction of granulomas areas, volumes and fibrosis. Furthermore, the present study concluded that PZQ still the more effective drug of schistosomiasis treatment than MZ. The silymarin is very useful in schistosomiasis treatment when combined with PZQ or MZ due to its anti-fibrotic effect.