The goal of the study is to evaluate the self-microemulsifying drug delivery system (SMEDDS) which enhances the oral bioavailability of the poorly water-soluble drug, total flavones of Hippophae rhamnoides (TFH). It is orally administered for the protection of human cardiovascular system. Self-microemulsifying time, particle size, polydispersity index (PDI), morphological characterization, in vitro dispersity, stability, in situ intestinal absorption and relative bioavailability were investigated in detail. The TFH-SMEDDS rapidly formed fine oil-in-water microemulsions with 0.1 mol x L(-1) hydrochloride solution, with average size of which was less than 40 nm, PDI was below 0.2, and the particles of which were observed round-shaped under transmission electron microscope. Almost 90% of TFH (expressed with quercetin) was released from SMEDDS within 20 min, which was remarkably higher than that from common capsules. The stability test showed the TFH-SMEDDS maintained stable in 6 months under accelerated condition. In situ absorption study demonstrated the absorption rate constant of TFH-SMEDDS (expressed with quercetin) was significantly higher than that of TFH in ethanolic solution (P < 0.05). The absorption of TFH from SMEDDS showed a 4.18-fold increase in relative bioavailability (expressed with quercetin) compared with that of the suspension. The results suggest that SMEDDS is a promising drug delivery system to increase the oral bioavailability of TFH.