Hepatic encephalopathy (HE) represents a diverse spectrum of complex neuropsychiatric disturbance resulting from liver disease and its concomitant metabolic and immunologic derangements.Hyperammonemia and inflammation cooperate to induce neurological alteration in hepatic encephalopathy. This study was conducted to elucidate the changes of serum, liver and brain proinflammatory cytokines in encephalopathy rats and to evaluate the hepato-protective activity of lactulose and/or taurine against thioacetamide (TAA) induced hepatic encephalopathy in rats. Acute hepatic encephalopathy (HE) in rats was induced by intraperitoneal injection of thioacetamide in 24 hours intervals for two consecutive days. The obtained results revealed a significant (p<0.05) increase in the levels of serum liver function tests (ALT, AST, ALP & bilirubin) in TAA rats group than those in control ones. In addition, the levels of ammonia and proinflammatory cytokines (IL-6, IL-1β & TNF-α) in serum, liver and brain were significantly (p<0.05) increased associated with a remarkable elevation in the level of serum S100β in TAA rats group. On the other hand, induction of hepatic encephalopathy caused a significant (p<0.05) decrease in albumin and total protein levels than those in control rats. When HE rats group was treated with lactulose or taurine and their mixture a considerable amelioration effects in all previous studied parameters were pronounced dependent on certain mechanisms.