The aim of this study was to examine if the liver damage caused by CCl 4 in combination with kava (Piper methysticum) could be alleviated via coadministration of sesame lignans. Six groups of male Sprague-Dawley rats were fed with corn oil as a control, kava only, kava plus sesame lignans, CCl4 only, CCl4 plus kava, and CCl4 plus kava plus sesame lignans, respectively. Body weight, diet intake, animal behavior, and serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were recorded along with the course. Four weeks later, organ weights and histopathological data including liver steatosis and fibrosis were obtained after sacrifice. At day 28, both the diet intakes and body weights of rats decreased, and their relative liver weights increased considerably in all three CCl4-treated groups compared to the control group. In accord with the levels of pathological steatosis and fibrosis, the liver damage caused by CCl4 was somewhat worse when kava extract was congested, but significantly attenuated when sesame lignans were coadministrated. No detectable liver damage was observed in the kava or kava plus sesame lignan group. The protective effect of sesame lignans against liver injury caused by CCl4 with or without kava extract was also observed in the relative activities of plasma ALT, AST and ALP. It is concluded that sesame lignans significantly alleviate liver damage of rats caused by carbon tetrachloride with or without kava. The potential risk of kava's hepatotoxicity can be greatly circumvented and the applications of kava may be further extended by coadministration of sesame lignans.