Background: Anti-schistosome vaccination is a necessary approach to minimize the hepatic vascular changes that lead to hepatic pathological consequences. Objective: To assess the prophylactic impact of soluble egg antigen (SEA) loaded on chitosan nanoparticles (ChNPs) on hepatic vascular and pathological consequences in experimental schistosomiasis. Material and Methods: Seventy male Swiss albino mice were classified into 7 groups; each of 10. G1: Non-infected control; G2: Infected control group; G3:  Injected by ChNPs then infected subcutaneously (SC) with S. mansoni cercaria; G4: Injected by Freund's Complete Adjuvant (FCA) then infected; G5: Injected by crude schistosomal egg antigen (SEA) combined with FCA (SEA-FCA) then infected; G6: Injected by SEA loaded on ChNPs (SEA-ChNPs) then infected; G7: Injected by both SEA-FCA + SEA-ChNPs then infected. Evaluation was done by parasitological, histopathological and immunohistochemical studies in murine models challenged by Schistosoma mansoni infection. Results: SEA-ChNPs was more successful in reducing stools and liver egg counts, hepatic granulomas number and size, improving hepatic architecture and vasculature, minimizing hepatic fibrosis, enhancing angiogenesis constructive impact, ameliorating adverse effects during fibrogenesis and remodeling of hepatic tissue by fibrosis degradation than SEA-FCA. Conclusion: ChNPs potentiated the protective and immune impact of SEA as proved by parasitological, histopathological and immunohistochemical assays; and confirmed its specific, marked, supportive and constructive effects on hepatic angiogenesis