Background: Portal endotoxemia has been speculated to be crucially involved in the pathogenesis of chronic hepatic inflammation which is highly associated with the development of type 2 diabetes mellitus (T2DM). This study examined whether portal endotoxemia was a pathogenic link between chronic subacute hepatic inflammation and systemic insulin resistance. Methods: Rats were randomly assigned into four groups: rats with intraportal saline or with three different doses of lipopolysaccharide (LPS) infusion for 4 wks. Pathological changes in the liver were evaluated via histological and biochemical examination. Systemic insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp by the tracer dilution method. Results: Body weight, fasting whole blood glucose, plasma insulin, triglyceride levels, mean arterial blood pressure and heart rate were not significantly changed in the four-week infusion period for all groups. The biochemical indicators of hepatic function such as aspartate aminotransferase, alanine aminotransferase and albumin were not changed during the observed period for all groups. During the euglycemic hyperinsulinemic clamp period, the ratio of glucose infusion rate to insulin level, an index of whole body insulin sensitivity, did not change among groups. Accordingly, insulin-suppressed hepatic glucose production and insulin-stimulated whole body glucose utilization also failed to change in any of the groups at the end of the study. The histopatholgical examination revealed that intraportal low-dose LPS infusion progressively enhanced the inflammatory changes of the liver in experimental rats in a dose-dependent manner. Conclusion: The present study suggests that mild portal endotoxemia could induce chronic low-grade hepatic inflammation but does not significantly affect systemic insulin sensitivity in the present experimental condition.