In clinical practice, Octreotide has its greatest impact in the management of bleeding varices. The present work is the first one which was undertaken to investigate the possible use of Octreotide as an antifibrotic agent and to study its effect on hepatic vasculature in Schistosoma mansoni infection. The material of this investigation consisted of two groups of albino mice (A&B) subdivided each, into normal control, infected control, Octreotide treated, Praziquantel treated and Octreotide with Praziquantel treated subgroups. Groups A & B were sacrificed at the 8th week and the 18th week post infection respectively. By analysis of the obtained results, Octreotide has induced reduction of the portal pressure, the weight of the spleen and the liver, the number of liver egg load, granuloma size and cellularity, and of the degree of hepatic fibrosis quantified by serum PIIINP, serum laminin and tissue collagen using sirius red dye assay. Moreover, the biochemical state of hepatocytes has been improved. The subgroups treated with Octreotide in association with Praziquantel revealed better results than the subgroups treated with Praziquantel alone. Data were analysed in terms of histological extent of liver fibrosis in sections stained with Masson trichrome and sirius red, hepatocytic and sinusoidal changes at an ultrastuctural level and by immunohistochemical demarcation of endothelial cells of blood vessels through the determination of factor VIII related antigen. The promising results detected in this study may encourage to further investigate the positive findings of this drug with the intention of its possible application on a clinical level.