Abstract: Hepatic affection by granulomatous inflammationin schistosomiasis suggested that a potential anti-pathologyvaccine could be generated based on limiting thepresence of hazardous hepatocytes induced apoptosis andcaused reduction of granulomas number and size. So, thiswork is concerned with experimental assessment of theefficacy of different Schistosoma mansoni antigens (SEA,SWAP and combined SEA and SWAP) on murine liverafter challenge by Schistosoma infection, histopathological,histochemical and molecular investigations were performedon sixty male laboratory bred Swiss Albino mice. Aschedule of vaccination and challenge infection was followedand performed on 6 mice groups (each of ten);control normal (G1), control infected (G2), adjuvantreceived then infected (G3), SEA + adj. received theninfected (G4), SWAP + adj. received then infected (G5)and SEA + SWAP + adj. received then infected (G6).Animals were euthanized 10 weeks post infection.Vaccination efficacy was assessed by histopathological,histochemical and molecular studies on murine hepatictissues. Results showed that:The combined (SEA + SWAP) antigens were better inreducing the number and diameter of the hepatic granulomas,with more protection of the hepatocytes DNA, inaddition to more decrease of hepatocytes induced apoptosisand fragmentation as demonstrated by molecular assay. Keywords Schistosoma mansoni _ Hepatocytes DNA _Induced apoptosis _ Fragmentation _ Molecular study.