Diabetes, characterized by chronic hyperglycemia, has reached serious epidemic proportions. It is also not infrequent to find increased incidence of liver injury in diabetics and hyperglycemia plays an important role in promoting liver injury through several mechanisms. The following review identifies the pathways through which hyperglycemia causes changes in liver of various animal models and liver cell culture models, and elucidates the mechanisms and consequences of hyperglycemia induced liver injury in humans. Some of the pathways which are hyperglycemia driven include increased oxidative and nitrosative stress, activation of stress signaling pathways and increased cytokine levels, impairment of protective mechanisms such as the expression of molecular chaperones and proteosome activity, and dysregulation of glucose and lipid metabolism. Thus, hyperglycemia induced changes in the livers cellular environment in in vitro and in vivo models have been documented extensively in the literature.