The retinoid X receptor (RXR) plays a critical role in transcriptional regulation via formation of an RXR homodimer or heterodimers with partner nuclear receptors. Despite the numerous beneficial effects, only a limited number of naturally occurring RXR agonists are known. In this report, two prenylated flavanones (1 and 2) isolated from Sophora tonkinensis were identified as new rexinoids that preferentially activated RXRs, relative to the retinoic acid receptor. The activities of 1 and 2 were the most potent among naturally occurring rexinoids, yet 2 orders of magnitude lower than the synthetic rexinoid bexarotene. Compounds 1 and 2 activated particular RXR heterodimers in a manner similar to bexarotene. A microarray assay followed by quantitative real-time polymerase chain reaction analyses on RNAs isolated from C2C12 myotubes treated with 1 or 2 demonstrated that they significantly increased mRNA levels of lipoprotein lipase, angiopoietin-like protein 4, and heme oxygenase-1. In contrast, bexarotene preferentially potentiated transcription of genes involved in lipogenesis and lipid metabolism such as sterol regulatory element-binding protein-1, fatty acid synthase, and apolipoprotein D by a liver X receptor agonist. In this study, we have demonstrated that two newly identified naturally occurring rexinoids, 1 and 2, possess properties different from bexarotene.