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Background and Aim: The prebiotic potential of lactulose is well known, but its effect to inhibit enteric bacterial dynamics and gut permeability has not yet been investigated in experimental studies. The present study aims to assess the effects of lactulose on the enteric bacterial dynamics gut permeability in a model of bile duct ligation in Wistar rats. Methods: Wistar rats were assigned into 3 groups, the Sham-operated control, bile duct ligated (BDL) and BDL+ Lac group on the 28 th day of bile duct ligation. Animals of BDL + Lac groups were treated with lactulose (1.0 g/kg), administrated by gavage, once a day for 7 days. Bacterial translocation into the organs and bacterial overgrowth as the indicators of the enteric bacterial dynamics and the levels of DAO and D-lactate as the biochemical makers of the gut permeability were measured in each group. Results: The bacterial colony forming units (CFU) in spleen and liver of BDL+Lac group was significantly decreased compared with BDL model group (P<0.01) and significant decrease of bacterial CFU was seen in the intestinal lavage in BDL+Lac group compared to BDL group (P<0.01). On the other hand, Lactulose revealed significant inhibitory effect as evidence by decreasing plasma DAO activity and D-lactate levels (P<0.01) in this model. Conclusion: These results indicate that lactulose can inhibit the enteric bacterial overgrowth, bacterial translocation (BT) and increasing gut permeability by opening the mucosa tight junction in ductal obstruction and obviate even systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) induced by obstructive jaundice.