Objective: Flavonoids are main active components of A. manihot, which can be transformed into glucuronide/sulfate conjugates in vivo. Exploring the pharmacokinetic profile of these conjugates is necessary to further elucidate the mechanism of action. Material and method: Flavonoid fraction of A. manihot (FFA) was extracted from A. manihot flower with ethanol. FFA (400 mg/kg) was orally given to normal rats and chronic kidney disease (CKD) model rats. Blood samples were collected at 5, 15, 30, 45, 60, 90, 120, 240, 360, and 720 min after administration. The plasma concentrations of quercetin and isorhamnetin glucuronide/sulfate conjugates were analyzed by UPLC-MS/MS. Results: In normal rats, AUC of quercetin-glucuronide conjugates, isorhamnetin-glucuronide conjugates, quercetin-sulfate conjugates, and isorhamnetin-sulfate conjugates was 459. 45 ± 192.70, 1153.01 ± 697.04, 417.81 ± 220.31, and 2475.19 ± 1085.22 mmol h/L, respectively. While AUC of quercetin and isorhamnetin was 5.47 ± 2.54 and 30.73 ± 25.95 mmol h/L. AUC of the glucuronide-sulfate conjugates of quercetin and isorhamnetin is 125-times higher than that of aglycone (quercetin and isorhamnetin), showing that glucuronide/sulfate conjugates represent the major circulating forms of A. manihot flavonoid in vivo. AUC of isorhamnetinglucuronide conjugates and quercetin-sulfate conjugates was 719.65 ± 619.22 and 275.49 ± 1 60.95 mmol h/L, indicating that less conjugated metabolites were formed in CKD rats compared with normal rats. The ratio of AUC glucuronide/sulfate /AUC aglycone decreased from 125 to 104, which implied the impaired phase II metabolism ability in CKD rat. Discussion and conclusion: Glucuronide-sulfate conjugates provide an important clue for further elucidating the activity of conjugated metabolites and their relationship with the nephroprotective efficacy of A. manihot. It is necessary to take caution when extrapolating pharmacokinetics parameters from healthy animals in designing pharmacological studies.