Background: Zerumbone (ZER) is a major bioactive compound of Zingiber zerumbet,a wild ginger plant that has been documented to have anti-proliferative, anti-inflammatory andanti-oxidant properties. To investigate its hepatoprotective potential, this study was designed todetermine the treatment effects of ZER on acute hepatotoxicity induced by paracetamol (PCM) inrats.Methods: The control group was administered with phosphate buffer solution (PBS) whilethe other two groups received PCM alone (1000 mg/kg) and PCM + 25 mg/kg ZER, respectively,at 0 h and 4 h after PCM injection. After 24 h, the blood and liver were collected for differentialwhite blood cell count, liver histological observation and biochemical analysis including alanineaminotransferase (ALT), aspartate aminotransferase (AST), and total protein concentration inserum and liver.Results: Treatment with ZER was found to significantly reduce ALT (P = 0.041), AST (P =0.044) and total hepatic protein (P = 0.045) in comparison to PCM-induced rats. Rats treated withZER exhibited the normal structure of hepatocytes with no vacuolisation or necrosis and showedsignificantly reduced neutrophil count (P = 0.037). This finding suggests its ability to suppress theinflammatory processes caused by PCM overdosage and decrease the hepatocytes tendency to gothrough necrotic processes.Conclusion: ZER possessed protective activity against PCM-induced acute hepatotoxicityin a rat model.