METHODS Xanthohumol (XN), a dietary flavonoid found in hops, may have health-protective actions against cardiovascular disease and type 2 diabetes. Yet, there are limited data on the pharmacokinetics (PK) of XN. This study provides PK parameters for XN and its major metabolites in rats. RESULTS A PK study was conducted in male jugular vein-cannulated Sprague-Dawley rats. Rats (n = 12/group) received an intravenous (IV) injection (1.86 mg/kg BW) or an oral gavage of a low (1.86 mg/kg BW), medium (5.64 mg/kg BW), or high (16.9 mg/kg BW) dose of XN. Plasma samples were analyzed for XN and its metabolites using LC-MS/MS. The maximum concentration (C(max) ) and area under the curve (AUC(0-96 h) ) of total XN (free and conjugated) were 2.9±0.1 mg/L and 2.5±0.3 h*  mg/L in IV group, 0.019±0.002 mg/L and 0.84±0.17 h*  mg/L in the oral low group, 0.043±0.002 mg/L and 1.03±0.12 h*  mg/L in the oral medium group, and 0.15±0.01 mg/L and 2.49±0.10 h*  mg/L in the oral high group. CONCLUSIONS The bioavailability of XN is dose-dependent and approximately 0.33, 0.13, and 0.11 in rats, for the low-, medium-, and high-dose groups, respectively.