AbstractAn inclusion complex formation with cyclodextrin is a promising method to improve the bioavailability of water-insoluble drugs. The pharmacokinetic characteristics ofHyperoside-2-hydroxypropyl-β-cyclodextrin inclusion complex in rats were evaluated. Compared withHyperoside, the results showed that maximum plasma concentration and AUC0-tindexes ofHyperosideinclusion complex in rat plasma were increased, the value of half-life time was prolonged, and the value of apparent clearance was decreased, which proved thatHyperosidecomplexed with 2-hydroxypropyl-β-cyclodextrin could improve its bioavailability and increase its blood concentration. Secondly, the therapeutic effect ofHyperosidebefore and after complexing was further compared through the dextran sodium sulfate-induced colitis in mice. The experimental results showed that under the same dose, theHyperosideinclusion complex had a better therapeutic effect, which could significantly increase the body weight of mice, improve the disease activity index, alleviate colon shortening, improve pathological colon changes, and have a better protective effect on colitis mice. According to 16S rDNA sequencing analyses,Hyperoside-2-hydroxypropyl-β-cyclodextrin may have an anti-inflammatory effect by increasing the abundance of beneficial bacteria (e.g. Firmicuria) and decreasing the proportion of harmful bacteria (e.g. Bacteroidetes) to balance the colon’s microbiota.