Diabetes mellitus (DM) is a serious metabolic disorder with micro and macro-vascular complications that result in a significant morbidity and mortality. The present study investigated the effects of Momordica charantia (M. charantia) on histological changes of the aorta and pulmonary trunk in streptozotocin-induced diabetic Wistar rats. Forty healthy adult Wistar rats of both sexes were randomly assigned into five groups A, B, C, D and E of eight rats each. Group A were the control (normal rats); B were the experimentally-induced diabetic rats; C were diabetic rats treated with methanolic extracts of M. charantia for two weeks (withdrawal group); D were diabetic rats treated with methanolic extracts of M. charantia for four weeks. E was diabetic rats treated glimepiride for four weeks. Tissues were harvested, processed routinely in paraffin wax and stained with routine and special stains. Histological results revealed morphological alterations in the aorta and pulmonary trunk of diabetic rats. Histochemical analysis also revealed abnormal deposition of glycogen in these vessels of diabetic rats. M. charantia and glimperide attenuated the morphological alterations and reduced the glycogen deposits. In conclusion M. charantia has a promising ameliorative effect on the morphology of the aorta and pulmonaty trunk in STZ-induced diabetic wistar rats and by extension, may be relevant in the management of cardiovascular alteration associated with DM.