Abstract: Background and Objective: It was reported recently that zerumbone (ZER), isolated from the rhizomes of a local plant Zingiber zerumbet, possesses intriguing bioactivities. The present studies investigate the effects of ZER on the liver of female Balb/c mice. Materials and Methods: In the acute and subacute dosing studies, twenty-four female Balb/c mice (14-19 g) were randomly divided into 4 groups (n = 6/group) and were given intraperitoneal (IP) doses of 0, 20, 100 and 250 mg/kg of ZER dissolved in 0.05 mL 5% ethanol (v/v). The animals were sacrificed 24 hrs post-treatment for hepato-histological and biochemical analysis. Acute study results showed no indication of liver toxicity or high plasma enzyme levels [Aspartate Aminotransferase (AST)] have been seen in all treated groups of mice. In the sub-acute study, dosing was once daily for 14 days consecutively. Changes in body weight and liver weight were recorded once in 2 days for each mouse. Results: The significant increase in body weights of all treated and control groups (p<0.05). In contrast, no significant difference in AST and relative liver weight has been observed in treatment compared to control groups (p>0.05). Histological analyses of the liver control group showed degenerative cell changes, moderate portal infiltration and mild lobular inflammation, while in treatment groups, livers showed few degenerative cell changes, moderate portal infiltration and mild lobular inflammation. Treatment groups showed few hepatocyte non-significant changes when compared to the control group (p<0.05). Conclusion: This investigation supports that the compound, ZER at 20 to 250 mg/kg dose, given daily for up to 14 days, had no ill effect on the livers of the female Balb/c mice.