OBJECTIVE: To study the effects of Glycyrrhiza uralensis on endogenous metabolites levels of triptolide (TPL) and triptonide (TPN) in rats. METHODS: 160 rats were given G. uralensis [30 g (crude drug)/kg] intragastrically, 2 h later given TPN (2.8 mg/kg) intraperitoneally for consecutive 30 d. 24 h urine were collected for 30 days, and then endogenous metabolites were separated and identified by column chromatograph and spectrum technology. UPLC-Q-TOF/MS was used to determine the common metabolites after giving TPL. 60 rats were randomly divided into TPL blank group, TPL group, G. uralensis+TPL group, TPN blank group, TPN group, G. uralensis+TPN group. Route of administration and dosage of treatment groups were same as above groups. TPL blank group and TPN blank group were given corresponding solvent, once a day, for consecutive 7 d. UPLC-Q-TOF/MS was used to determine the endogenous metabolites of TPL and TPN in rats. RESULTS: Five endogenous metabolites were isolated and identified from urine of rats after given TPN, as 1-methylhydantoin, methyl 4-aminonicotinate, 3,4-dihydro-6-hydroxy-2(1H)-quinolinone, 2,6-quinolinediol, 2-quinolone, respectively. Those five metabolites were also found in urine of rats after giving TPN. 1-methylhydantoin in TPL group and 2,6-quinolinediol in TPN group were significantly increased, compared with TPL blank group or TPN blank group (P<0.05); while urine levels of 1-methylhydantoin and 2,6-quinolinediol decreased after TPL or TPN combining with G. uralensis, compared with TPL/TPN blank group, with no significant difference (P>0.05). CONCLUSIONS: The above five endogenous metabolites were isolated from rat urine after given TPL or TPN for the first time. The levels of 1-methylhydantoin after giving TPL and 2,6-quinolinediol in urine after giving TPN can be recovered by G. uralensis.