In this article, the impact of dietary lipids and heterotopic heart transplant procedures on the structure and morphology of several tissues in apolipoprotein E-knock out (apo E-KO) mice is reported. In particular, addition of dietary cholesterol, plant sterol or either changes in hemodynamic factors or immunological responses after heart transplant procedures are associated with histological and cytological changes in the kidneys, skin, heart and arteries in this animal model. In this report, alterations in the vessel wall structure and morphology including formation of atherosclerotic plaques, infiltration of macrophages, as well as evidence for rejection of the donor hearts and formation of non-specific vacuolation in the liver and kidney have been illustrated. In conclusion, various factors may cause changes in tissue structure and morphology which may lead to tissue dysfunction. Early detection of such changes and appropriate remedies including dietary and lifestyle modifications may help sustain tissue structure and function.