Background: Hepatic encephalopathy (HE) is a major health concern worldwide with a significant morbidity and mortality in addition to the economic burden. Oxidative stress, induced from exposure to various pollutants, with the resultant inflammation contributed to the pathogenesis of HE. This study was conducted to evaluate the antioxidant and anti-inflammatory effects of rosemary ethanolic extract on thioacetamide (TAA) induced HE. Methods: Rats used in this study were divided into three groups: control group, TAA group received intraperitoneal (i.p) injection of TAA twice weekly for 12 weeks, rosemary treated group received i.p injection of TAA twice weekly and oral daily dose of rosemary ethanolic extract for 12 weeks. Results: The results revealed an obvious state of oxidative stress in liver and brain as evidenced by elevated malondialdehyde (MDA) and oxidized glutathione (GSSG) levels and lowered reduced glutathione (GSH) and total antioxidant capacity (TAC). Additionally, the concentration and gene expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) indicating a significant inflammatory response. On the other hand, co-treatment with rosemary extract exhibited a significant improvement antioxidant capacities and inflammatory status of liver and brain. Moreover, the matrix metalloproteinase-1 (MMP-1) and paraoxonase-1 (PON-1) as fibrotic markers were analyzed proposing a possible anti-fibrotic activity of rosemary. Conclusion: it can be concluded that rosemary extract provide a powerful ameliorating effect against TAA induced HE owing to the antioxidant, anti-inflammatory and possible anti-fibrotic activities of its constituents.