Liver is the primary organ for glucose metabolism. Apart from expressing the enzymes involved in glucose metabolism and regulation, liver possesses numerous enzymes involved in detoxification and toxicity enhancement (Phase I and Phase II). Also, most substances, upon entry into the body are primarily subjected to metabolism in the liver. Non-alcoholic fatty liver disease, a spectrum of liver damage that ranges from relatively benign hepatic steatosis to potentially fatal cirrhosis is very closely associated with Type 2 diabetes. The clearance of 4-hydroxynonenal, a major product of lipid peroxidation, by the enzymes Glutathione-S-Transferase (GST), Aldehyde Dehydrogenase (ALDH), and Alcohol Dehydrogenase (ADH) was impaired in liver microsomes and mitochondria of BB/WOR diabetic rats. As evidenced through the many studies utilizing in vivo animal models and in vitro models of hepatocytes and HepG2 cells, metabolism of high concentrations of glucose in liver may impair several cellular processes thus leading to injury.