Abstract: Comparative histopathological and histochemical studies on the gut damage following infections with Schistosoma mansoni and Schistosoma margrebowiei were showed after 42, 49, 77, 91, 105 and 119 days post infection (d.p.i) in definitive host mouse. The prominent histopathological changes were thinning of epithelial cells and variable shape of the goblet cells. Most of the villi were shrunken, crackling and tips were damaged. Increases spaces and infiltration of the granulocytes were observed in lamina propria of the tunica mucosa. The granulomas with single or multiple eggs were mainly surrounded by variety of connective tissues observed in the submucosa, tunica muscularis and tunica serosa from 42 to 119 d.p.i. in S. mansoni and in S. margrebowiei from 77 to 119 d.p.i. S. mansoni eggs produced a minimum cellular reaction in the lamina propria of tunica mucosa from 91 to 119 d.p.i. A few eggs were seen in the blood vessels of the submucosa from 42 to 119 d.p.i. in S. mansoni. Due to infections swollen walls with enlarged endothelial cells of the blood vessels were observed. Fibrosis was seen in the tunica muscularis and tunica serosa from 91 to 119 d.p.i. A few areas of early necrosis were also observed in the tunica submucosa and tunica muscularis from 91 to 119 d.p.i. in both parasite species. Normal and infected brush borders, epithelial cells, goblet cells, muscular cells, connective tissues in the lamina propria of tunica mucosa and submucosa were positive for protein. The most prominent changes were increase of protein in paneth cells present in the crypts of gut during infections. Significantly increased amount of glycogen and acid mucopolysaccharides was observed in the goblet cells. Thin granules of glycogen were positively stained in the brush borders and also muscular cells of the tunica muscularis. Ribonucleic acid was stained positively in epithelial cells, connective tissues and muscular cells. Endothelial cells were stained weekly for ferric irons and lipofuscin pigments.