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.