Abstract: 5-Hydroxytryptamine 2C (5-HT_2C) receptor is one of the major targets of anti-obesity agents, due to its role in regula-tion of appetite. In the present study, the 70% EtOH extract of the roots of Bupleurum chinense was revealed to have agonistic activity on 5-HT_2C receptor, and the subsequent bioassay-guided isolation led to identification of several saikosaponins as the active constitu-ents with 5-HT_2C receptor agonistic activity in vitro and anti-obesity activity in vivo. The new compound, 22-oxosaikosaponin d ( 1 ), was determined by extensive spectroscopic analyses (HR-ESI-MS, IR, and 1D and 2D NMR). The primary structure-activity relation-ship study suggested that the intramolecular ether bond between C-13 and C-28 and the number of sugars at C-3 position were closely related to the 5-HT_2C receptor agonistic activity. Saikosaponin a ( 3 ), the main saponin in B. chinense, showed obviously agonistic activity on 5-HT_2C receptor with an EC₅₀ value of 21.08±0.33 μmol·L^-1 in vitro and could reduce food intake by 39.1% and 69.2%, and weight gain by 13.6% and 16.4%, respectively, at 3.0 and 6.0 mg·kg^-1 in vivo. This investigation provided valuable information for the potential use of B. chinense as anti-obesity agent.