Hederasaponin C (HSC), one of the main components of Pulsatilla chinensis, is considered as a potential drug for the treatment of inflammatory bowel disease. In the present research, we developed a pharmacokinetics–pharmacodynamics model to describe the concentration–effect course of drug action following the intraperitoneal injection of HSC in colitis rats. A sensitive UPLC–MS/MS method was established for the the determination of HSC in rat plasma to explore the pharmacokinetics properties. The separation was performed on an Accucore C18 column (2.1 × 100 mm, 2.6 μm) with a flow phase consisting of acetonitrile and 0.1% formic acid water. The assay method was validated and demonstrated good adaptability for application in the pharmacokinetics study. Then the levels of tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β) in colon tissues were measured using an ELISA assay. The levels of TNF‐α, IL‐1β and IL‐6 were decreased after HSC administration, suggesting that HSC can significantly improve the level of inflammatory syndrome factor. The pharmacokinetics study showed that the time to peak concentration of HSC was 1 h. The concentration–effect curves showed a hysteresis loop. There was also a hysteresis between the peaked concentration and the maximum effect of HSC. The present study established in vivo pharmacokinetics–pharmacodynamics models and the results showed a great potential of HSC for treating ulcerative colitis.