This study aimed to investigate the effect of mannan-oligosaccharide (MOS) on the lipogram and selected organ functions in hyperlipidemic rats. Animals were subjected to different treatments for 60 days. Balanced basal diet was supplied to control rats; saturated high fat- and/or MOS-contained diets were supplied to tested rats. Sera were collected on escalating times and total lipids, cholesterol, triacylglycerols, HDL-C, LDL-C, VLDL-C, AST, ALT, urea and creatinine were evaluated. On the last day, rats were sacrificed and the kidneys, liver, heart with aorta were picked out for histopathology. The results of MOS-treated group revealed significant decrease in total lipids, cholesterol, LDL-C, VLDL-C, AST, ALT, urea and creatinine with significant increase in HDL-C. Histopathological findings in the tested organs have been ameliorated with MOS, comparing with those in hyperlipidemic rats. The obtained data may give MOS the potential of antihyperlipidemic activity for prophylaxis and treatment of hyperlipidemia and related diseases.