The aim of the present study was to find a way of prepare silybin-phospholipid complex to make oral bioavailability of silybin increase and to study its physicochemical properties and to compare the pharmacokinetic characteristics and bioavailability after oral administration of silybin-phospholipid complex and silybin-N-methylglucamine in rats. Using ethanol as a reaction medium, silybin and phospholipids were resolved into the medium, after the organic solvent was removed under vacuum condition, silybin-phospholipid complex was formed. The new complex's physicochemical properties including scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), solubility, dissolution, etc., were tested. The concentrations of silybin after oral administration of silybin-phospholipid complex and silybin-N-methylglucamine at different time in rats were determined by RP-HPLC. The pharmacokinetic parameters were computed by software program 3p97. Our data showed that silybin and phospholipids in the silybin-phospholipid complex were combined by non-covalent-bond, not forming a new compound and the solubility of silybin-phospholipid complex in water and in n-octanol was effectively enhanced. We found that mean plasma concentration-time curve of silybin after oral administration of silybin-phospholipid complex and silybin-N-methylglucamine in rats was both in accordance with open single-compartment model with first-order absorption. Pharmacokinetic parameters of silybin in rats were Tmax 10 and 5 min; Cmax 126.72 and 104.29 ng ml(-1); AUC(0-infinity) 1020.33 and 235.81 ng ml(-1)h, respectively. The bioavailability of silybin in rats was increased remarkably after oral administration of silybin-phospholipid complex comparing to silybin-N-methylglucamine. This was mainly due to an impressive improvement of the lipophilic property of silybin-phospholipid complex and improvement of the biological effect of silybin.