In Ethiopian traditional medicine the aqueous decoction of the leaves of Cineraria abyssinica Sch. Bip. exA. Rich (Asteraceae) is used for the treatment of various ailments including liver diseases, however, to date, there appears to have been no scientific report on the phytochemistry and claimed hepatoprotective activity of the plant. The main purpose of this study was, therefore, to carry out hepatoprotective and antioxidant activities of the leaf extracts of C. abyssinica. Hepatoprotective activities of the aqueous and 80% methanolic extracts as well as the methanol fraction of the leaves of C. abyssinica were investigated against carbon tetrachloride-induced liver damage in rats. Intraperitoneal administration of 2 ml/kg of CCl4 (50% in liquid paraffin) significantly (p < 0.001) raised the plasma levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT ) and aspartate aminotransferase (AST) in the toxin group compared with the values in the control group. Pretreatment of rats with 200 mg/kg of the aqueous, 80% methanol extracts and the methanol fraction reduced the toxin-induced rise in plasma ALP (65%, 75.4%, 85%), ALT (46.1%, 42.3%, 75%), and AST (58%, 98%, 79%), respectively. The standard drug, silymarin (100 mg/kg) reduced serum ALP (88%), ALT (92%), and AST (87.3%). Bioactivity-guided fractionation of the methanol fraction resulted in the isolation of the flavonol glycoside rutin, whose structure was assigned on the basis of spectroscopic methods. The results of biochemical analysis were further verified by histopatholgical examination of the liver, which showed improved architecture, absence of necrosis and a decrease in inflammation, compared with the findings in the toxin group of animals. Both the extracts and rutin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities. Acute toxicity studies showed that the total extracts of the plant are nontoxic up to a dose of 3 g/kg. The present study revealed for the first time the presence of a hepatoprotective and antioxidant phytochemical in the leaves of C. abyssinica that scientifically validates the traditional use of the plant and its potential for the treatment of liver disorders.