Background: Sepsis related-multiple organ dysfunction is associated with ileum injury. We aimed to determine the causes of ileal injury in two models of microbial sepsis resulted from infection with Aeromonas hydrophila or its endotoxin. We also evaluated the protective effect of phytic acid. Methods: Thin sections of ileum from 60 Swiss male mice in control, bacteria-infected or lipopolysaccharides (LPS) and bacteria-infected or LPS-infected co-administered with phytic acid were subjected to histopathological and TdT-mediated dUTP nick-end labeling (TUNEL) assay for apoptotic cells detection while ultra thin sections were stained with uranyl acetate and lead citrate for cytological changes examination. Also, ileum images were exposed to the image analysis software to determine some related morphometric measures. Results: Necrosis and apoptosis were observed in ileum injury in both examined sepsis models. The ileum injury was more severe in LPS model. Phytic acid showed the ability to attenuate ileum injury in Aeromonas hydrophila and its endotoxin models of sepsis after four weeks administration where its supplementation significantly minimized the histopathological and cytological complications and morphometric alterations resulted from the injury. Conclusion: The protective effects of phytic acid may be caused by increased mucous secretion, decreased apoptotic index, attenuating the inflammatory and lymphocytic cells count or increasing the renewal of the crypt cells and villous epithelial cells proliferation.