This study aims to investigate the possible hepato-protective effects of honokiol against liver damage and cirrhosis induced by carbon tetrachloride (CCl4) in the rat. Rats were treated acutely, or chronically with CCl4 at 5 day intervals (0.06 mL/100 g body weight, administered as 50% vol/vol solution in liquid paraffin) by gavage, in combination with phenobarbitone in drinking water (0.5 g/L for 7 days prior to, and during CCl4 treatment) to induce liver damage. Some were also co-treated with 0.1 mg/kg or 0.03 mg/kg honokiol (i.p.) or with appropriate vehicle. In vivo measurement of the liver sinusoidal area was performed using confocal microscopy following i.v. fluorescein isothiocyanate (FITC) dextran. Liver histology and function tests were performed, and liver and body weights were measured. Confocal microscopy showed that acute and chronic CCl4 treatment significantly reduced the sinusoidal area. Honokiol (0.1 mg/kg, but not 0.03 mg/kg) partially reversed the decrease in the sinusoidal area after acute or chronic treatments with CCl4. Acute and chronic CCl4 treatment produced significant histological liver damage. Honokiol (0.1 mg/kg) significantly reduced the histological damage caused by chronic treatment. Chronic treatment with CCl4 caused a significant increase in the bilirubin level that was not observed following the high dose of honokiol (0.1 mg/kg). In conclusion, this study showed that honokiol exhibits potent hepato-protective effects in rats treated with CCl4. Copyright (c) 2005 John Wiley & Sons, Ltd.