Chronic hepatic encephalopathy (CHE) is a multifactorial disease. The presence of central nervous system (CNS) and systemic oxidative stress (OS) is thought to contribute to the pathogenesis of CHE. Clinically, it is known that peripheral inflammation contributes to acute worsening of patients with CHE. We used in-vivo 1H-MRS, ex-vivo/in-vitro ESR and histology of CNS to investigate longitudinally the course of OS in the rat model of CHE. Our studies revealed antioxidant system impairment (decrease of CNS Asc and GSH, post-BDL) and increased CNS and systemic OS over the course of CHE progression, concomitant with CNS Gln and systemic NH4+ increase.