The aim of this study was to investigate the effect of naringin on the bioavailability and pharmacokinetics of tamoxifen and of its metabolite, 4-hydroxytamoxifen in rats. The pharmacokinetic parameters of tamoxifen and 4-hydroxytamoxifen were determined by HPLC after pretreating with naringin (1.5, 7.5, and 15 mg/kg) 30 min before orally administering tamoxifen (10 mg/kg). Compared with the control group (treated with tamoxifen alone), naringin pretreated animals showed significantly (p<0.01) increased areas under the plasma concentration-time curves (AUC) and peak tamoxifen concentrations (Cmax). The absolute bioavailabilities (AB%) of tamoxifen in naringin pretreated animals were enhanced versus control (from 32.8% to 47.1%), and the relative bioavailabilities (RB%) of tamoxifen in the naringin pretreated groups were 2.02-2.88 times higher than that in the control. No significant changes in the terminal half-life (t(1/2)) or Tmax of tamoxifen were observed in the naringin pretreated groups. The AUCs of 4-hydroxytamoxifen after pretreating naringin were also significantly elevated (p<0.05) versus the control. But metabolite ratios (MR; AUC of 4-hydroxytamoxifen to tamoxifen) were significantly lower. These results suggest that the enhanced bioavailability of tamoxifen in the presence of naringin might be due to the inhibition of CYP3A4 by naringin. If the results of this study are further confirmed by clinical trials, tamoxifen dosages should be adjusted to avoid potential drug interaction when tamoxifen is used clinically in combination with naringin-containing dietary supplements.