Background: Fulminate hepatic failure (FHF) is a serious condition with very high mortality. A practical liver support system for patients in (FHF) remains a needed therapeutic modality. An extracorporeal bioartificial liver might be an appropriate treatment, since it can provide liver-specific functions, maintain the patient alive and allow spontaneous recovery of patients own liver or act as bridge toward liver transplantation.Methods: We have established a model of acute liver failure in rats by administration of D-galactosamine. The animal model was used to evaluate a bioartificial liver (BAL) based on viable hepatocytes. We have isolated normal hepatocytes by a modified collagenase perfusion technique from 18 male golden hamsters (150-250 gm). The average % viability of hepatocytes in our experiment had been about 90% determined by trypan blue exclusion. Cells were immobilized in a membrane-coated alginate gel beads to form micro-encapsulated hepatocytes, which were subsequently inoculated into the bioreactor. BAL contained 10 ml of hepatocyte suspension with approximately 10.107 viable microencapsulated hepatocytes. 80 adult white male rats 6-8 week old (Wt = 150 – 250 gm) were studied. 60 rats were administered D-galactosamine (0.5 gm/kg) intraperitoneally and divided into three experimenal groups: positive control group (GII n = 20) received only 20% dextrose infusion (0.2 to 0.7 ml/hr) via venous blood line to prevent hypoglycemia, device control group (GIII n=20) connected to empty BAL and treated group (GIV n =20) connected to BAL with microencapsulated hepatocytes. The other 20 rats did not receive D-gal (normal rats) connected to BAL with micro encapsulated hepatocytes for 2 hours to test safety and tolerability of the animals to BAL treatment considered as negative control (GI n = 20). Hemoperfusion through BAL was carried for 2 hours in treated animals 24 hours after injection D-gal. Main outcome parameters were survival, neurologic status and histopathologic exam as well as laboratory parameters (prothrombin time, serum bilirubin, ALT, AST and blood ammonia) were measured at 0, 24, 48 and 72hrs after injection of D-gal.Results: All experimental animals developed evidence of liver failure at 24hrs after injection of D-gal as evidenced by prolonged prothrombin time, marked hepatocellular enzymes elevation as well as blood ammonia, serum bilirubin and microscopic massive hepatocyte necrosis. Survival of FHF rats connected to BAL with microencapsulated hepatocytes (GIV) was significantly increased when compared to control groups (II and III). 55% of treated animals had survived (p<0.001). All BAL treated animals GIV experienced neurological improvement. Histopathology of the animals that died 72hrs of D-gal showed massive centrilobular necrosis. In contrast, the histology of the survived animals in GIV was almost normal when compared to negative control group. All laboratory parameters showed significant improvement in BAL treated GIV when compared to GII, III.Conclusion: D-galactosamine rat liver failure model is effective in testing hepatocyte-based extracorporeal support, which can provide metabolic support, increases survival and allows recovery in rats with FHF.