A B S T R A C TThe present study was designed to elucidate the protective effect of subsequent pretreatment with Fructus Piperis Longi extract in liver and brain tissue of experimental rats exposed to Hepatic encephalopathy induced by intraperitoneal administration of TAA. Plf extract (50 mg/kg) was force-fed to rats every day, 7 days before administration of Thioacetamide. Thioacetamide 200 mg/kg was intraperitoneally administered to rats twice per week for four weeks. Administration of Plfext was extended during Thioacetamide. After 4 weeks, animals were sacrificed. Biochemical parameters in serum and homogenized liver and brain were tested. A significant increase in serum transglutaminase, alkaline phosphatase and gamma glutamyl transferase activity and plasma ammonia, a significant decrease in serum albumin and total protein was recorded in the liver of Thioacetamide-treated rats. Significant increases in liver and brain lipid peroxides associated to significant decreases of liver and brain reduced glutathione concentration and catalase activities were also recorded. Administration of Plfext treatment reduced the severity of liver fibrosis and oxidative damage which was substantiated by improvement of liver function detected by a decrease in serum aspartate amino transaminase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and increase in total protein and Albumin. It was concluded that treatment of the ethanolic extract of Fructus Piperis Longi enhance Liver and brain parameter and enhanced antioxidant activities of liver and brain.