In the present study, we compared the systemic exposure of scutellarin following intraportal with intravenous administration to understand the contribution of presystemic hepatic elimination to the low oral bioavailability. Results showed that the hepatic first-pass elimination of scutellarin played an insignificant role in the presystemic elimination of orally administered scutellarin. Moreover, our results suggested that the site of first pass extraction was not the liver, but the gastrointestinal tract.