In this study, the physiological and molecular effects of two cholesterol lowering agents , synthetic statin (atorvastatin) and natural statin (simvastatin) on diabetic and hypercholesterolemic adult male Wistar albino rats (Rattus norvegicus)at two doses, 10 and 40 mg/kg, for 8 weeks was investigated. Other physiological parameters were evaluated under this investigation, like: glucose, urea, uric acid, creatinine, total protein, albumin, globulin, A/G ratio, total, direct and indirect billirubin) To assess the beneficial effect of the drugs on liver genomic DNA, the (RE) analysis with 5 restriction endonucleases manifested variations in DNA digestion patterns in diabetic and hypercholesterolemic rats treated with atorvastatin and simavstatin. Such variation reflects and clarifies a restoration and repairing effect of statin on rat liver DNA in diabetic and hypercholesterolemic rats.