Background and aim:Studies have shown that polymethoxylated flavones have potent hypolipidemic properties. There are, however, gaps in the literature on their effects on organ structures. This study evaluated the histopathological effects of Ortanique peel polymethoxylated flavones extract (PMF ort ) on the organ structures of diet-induced hypercholesterolemic rats. Methods: Thirty Sprague-Dawley rats were fed normal rat chow as well as high cholesterol diets supplemented with PMF ort and niacin, respectively. Light microscopic evaluation of the liver, spleen, kidney and bowel of hypercholesterolemic rats fed PMF ort and niacin was performed to determine possible morphologic alterations, compared to untreated hypercholesterolemic rats. Results: Untreated hypercholesterolemic rats showed significantly altered intestinal morphology, with an increase in the number of absorptive cells and in villus length when compared to untreated normal rats. They also exhibited hepatic steatosis (100%) and inflammation (20%) and lymphoid hyperplasia of the spleen (33%). Hypercholesterolemic rats treated with 1.5% PMF ort showed reductions in absorptive cell number, villus length and hepatic steatosis compared to the untreated hypercholesterolemic rats. They also showed significant reduction in splenic lymphoid hyperplasia. Conclusions: The current results would suggest that PMF ort consumption has no toxic effects on the organs of hypercholesterolemic rats but may ameliorate hypercholesterolemia-associated alterations in organ structures.