Schistosomiasis constitutes one of the major endemic diseases in both African and Asian countries. There are numerous strains of Schistosoma mansoni. Although there is similarity between their life cycles, yet there are many differences in the morphology of the adult worms, their pathogenecity, their infectivity and their ultrastructural features. This study was performed on albino mice infected with both Egyptian and Saudi strains, to investigate the characteristic differences between them. It was found that at the eight week post-infection, the highest amount of egg deposition and granuloma formation was present in the liver of infected mice with the Egyptian strain; while it was highest in the small intestine of those infected with the Saudi strain, followed by the liver and the large intestine. Although no prominent histopathologic differences were detected in the cellular and tissue reactions in the resulting granulomata surrounding eggs, yet marked differences were observed in the surface topography of the tegument and distribution of papillae, pattern of ridges, microvilli, and spines of both strains. These differences were more pronounced in males. It might be concluded from this study that such differences are due to strain variation, biological and morphological characteristics of Schistosoma mansoni, and could be considered as a baseline for further experimental studies.