Hepatic encephalopathy (HE) is a common and severe complication of liver failure. The pathogenesis of HE is linked with gut-derived ammonia (NH3). The standard care for patient experiencing episodes of HE is lactulose but observance is poor due to uncomfortable side-effects. Rifaximin is a potent candidate but there is no clinical study that assess its efficiency solely. This study aim to assess, in a bile-duct ligation (BDL) model of HE, the efficiency of rifaximin to reduce plasma NH3 and ameliorate HE status. 3 wks after BDL surgery, all animals were sorted in 5 grps: SHAM-Veh, BDL-Veh, BDL-Lac, BDL-Rif, BDL-Lac+Rif. Ttm was given by gavage for 3 wks with vehicle, lactulose, rifaximin and the combination of both ttm. Survival, body-weight, food consumption and body composition was assess every wk. During the ttm, behavioral analysis was done to assess the HE status, including OFT, EPM, Rotarod, NOR and night activity. At the end of the study, brain water was measured and plasma sample was taken. No difference was seen in the survival, growth, food consumption or body composition between BDL-grps. In the last wk the free water was increased in all BDL rats. No difference was seen in any grps regarding behavioral tests nor was any evidence of brain edema. NH3 level was increased in BDL treated with either lactulose or rifaximin compare to SHAM but surprisingly not with vehicle. The biochemistry parameters confirm the onset of cirrhosis in BDL grps. This study don’t present strong, reliable and sufficient data to conclude on the efficacy of rifaximin. Future direction will aim to increase the dose of drug; reduce the duration of the model; trigger an episode of HE before ttm.