Peripheral insulin-resistance and impairment of the hepatocellular function are two major possible causes of diabetes mellitus in liver cirrhosis. The pathogenesis of insulin-resistance (receptorial or post-receptorial) is unknown but it represents an important complication because it has a profound impact on the pathology and natural history of the liver disease. The beta-cell capacity, to compensate the insulin-resistant state to avoid the onset of frank diabetes mellitus plays a critical importance. Many factors may induce a reduction of the beta-cell function in patients with liver cirrhosis: some are due to a predisposition to the development of diabetes: genetic or environmental, unrelated to the hepatic disease; some others are hepatic disease-dependent (excess liver and islet of Langerhans iron deposition, HCV infection rather than other hepatic infections, the co-presence of HCC) and may be crucial because additive to the previous. It is likely that the high prevalence of diabetes in liver cirrhosis is due to the early onset of strong insulin-resistance coupled to a deficient beta-cell function aggravated by hepatic disease-related factors.