The primary aim of this study was to investigate the effects of Ortanique peel polymethoxylated flavones extract (PMF^ort) on organ function parameters in the serum of hypercholesterolemic and normal rats. Thirty Sprague–Dawley rats were fed high cholesterol diets supplemented with 1.5% PMF^ort and niacin respectively for 49days. Hypercholesterolemic rats fed PMF^ort had significant reductions in the activities of aspartate aminotransferase and alkaline phosphatase (69.12±3.34 and 87.22±8.42U/L respectively) compared to the untreated hypercholesterolemic group (118.61±4.85 and 132.62±10.62U/L respectively, p<0.05). Supplementation of the diet with niacin or PMF^ort resulted in no significant differences in the serum levels of creatinine or urea in any of the groups. Total bilirubin was highest in the untreated hypercholesterolemic group. Supplementation of the diets of hypercholesterolemic rats with PMF^ort resulted in significant reductions in the activities of serum creatine kinase and lactate dehydrogenase (119.3±25.3; 222.5±50.3U/L, p<0.05) respectively relative to the untreated hypercholesterolemic group (257.2±48.3; 648.8±103U/L, p<0.05). The results would suggest that PMF^ort modulates hypercholesterolemia-associated organ injury in rats. PMF^ort could therefore be a suitable candidate for prophylactic and therapeutic treatment of hypercholesterolemia-associated organ injury.