PURPOSE: In this study, the effect of polyamidoamine (PAMAM) dendrimers on the solubility of silybin was investigated. The in vitro drug release and the pharmacokinetics of silybin-dendrimer complex were also investigated. METHODS: The solubilization of silybin by PAMAM dendrimers of generation G1.5, G2, G2.5, and G3 with different concentrations was determined and compared in different pH conditions. The in vitro release of silybin from the silybin-dendrimer complex was compared with pure silybin. Twelve rats randomized into two groups were separately orally administered silybin and silybin-PAMAM complex. RESULTS: The water solubility of silybin was significantly improved by PAMAM dendrimers of generations G1.5, G2, G2.5, and G3 with different concentrations in different pH conditions (P < 0.05). The in vitro release of silybin from the silybin-dendrimer complex was significantly slower compared with pure silybin (P < 0.05). The pharmacokinetics parameters T (max), C(max), and AUC(0-∞) of silybin and silybin-dendrimer complex were 10 minutes, 134.2 ng/mL, 654.6 (ng·h)/mL and 15 minutes, 182.4 ng/mL, 1298.7 (ng·h)/mL, respectively. The relative oral bioavailability of silybin-dendrimer complex calculated on the basis of AUC(0-∞) was about 178% as compared with silybin. CONCLUSION: These results indicated that PAMAM dendrimers could increase the water solubility of silybin and improve its oral bioavailability.