In this study, metabolism of nobiletin in rats was studied using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS).  As a result, seven major metabolites were found in bile, urine and serum of rats.  Three phase I products were assigned to be demethyl and di-demethyl products, and other four phase II products were assigned to be glucuronic and sulfonic conjugates.  The four phase II metabolites were reported for the first time.  Among the metabolites found in the present study, the glucuronic conjugates of demethyl-nobiletin played a predominant role in the metabolic pathway, indicating that its potential role for glucuronidation-related factors, such as gene polymorphism, drug-drug interaction, etc., in changing the active and toxic effect of nobiletin and that it should be paid more attention in further development.