Objective. Fulminant hepatic failure (FHF) is a clinical syndrome of sudden and severe liver dysfunction accompanied by encephalopathy in a previously healthy person. In FHF, hepatocytes are severely damaged and ordinary liver regeneration is impaired. We demonstrated that the expression of osteopontin (OPN), a multifunctional cytokine, was up-regulated in mouse oval cell (a stem-cell progenitor) induction models. Material and methods. Based on this finding, serum OPN levels were examined in 43 patients with FHF and in 45 patients with acute self-limited hepatitis (AH). To determine the cellular source of OPN, the expression of OPN was studied in a liver specimen derived from an FHF patient. Results. The mean OPN level of patients with FHF was 2.80±0.48 ng/ml (log10,±SD), which was significantly higher than that of the patientswith AH (2.42±0.39 ng/ml) (p = 0.003, unpaired t-test). Patients with elevated serum OPN levels had a significantly poorer prognosis than patients whose serum OPN levels were not elevated. In the FHF patient’s liver, OPN protein was expressed not only in inflammatory cells but also in regenerating hepatocytes and bile ductular structures. Conclusions. Our current study indicates that serum OPN levels increased in patients with FHF and that OPN might play an important role in liver regeneration due to activation of hepatic stem cells. Objective. Fulminant hepatic failure (FHF) is a clinical syndrome of sudden and severe liver dysfunction accompanied by encephalopathy in a previously healthy person. In FHF, hepatocytes are severely damaged and ordinary liver regeneration is impaired. We demonstrated that the expression of osteopontin (OPN ), a multifunctional cytokine, was up-regulated in mouse oval cell (a stem-cell progenitor) induction models. Material and methods. Based on this finding, serum OPN levels were examined in 43 patients with FHF and in 45 patients with acute self The absolute OPN level of patients with FHF was 2.80 ± 0.48 ng / ml (log10 , ± SD), which was significantly higher than that of the patients with AH (2.42 ± 0.39 ng / ml) (p = 0.003, unpaired t-test). Patients with elevated serum OPN levels had a significant poorer prognosis than patients whose serum In the FHF patient’s liver, OPN protein was expressed not only in inflammatory cells but also in regenerating hepatocytes and bile ductular structures. Conclusions. Our current study indicates that serum OPN levels increased in patients with FHF and that OPN might play an important role in liver regeneration due to activation of hepatic stem cells.