Inhibition of protein tyrosine phosphatase-1B (PTP1B) has been proposed as a therapy for treatment of type-2 diabetes and obesity. Bioassay-guided fractionation of an EtOAc-soluble extract of the root bark of Erythrina mildbraedii, using an in vitro PTP1B inhibitory assay, resulted in the isolation of three new isoprenylated flavonoids, abyssinone-IV-4'-O-methyl ether (2), 7-hydroxy-4'-methoxy-3'-(3-hydroxy-3-methyl-trans-but-1-enyl)-5'-(3-methylbut-2-enyl)flavanone (3), and abyssinone-VI-4-O-methyl ether (6), along with six known flavonoids, abyssinone-V-4'-O-methyl ether (1), abyssinone-V (4), abyssinone-IV (5), sigmoidin E (7), 4'-hydroxy-5,7-dimethoxyisoflavone (8), and alpinumisoflavone (9). Compounds 1 and 2, 4-7, and 9 inhibited PTP1B activity, with IC50 values ranging from 14.8 +/- 1.1 to 39.7 +/- 2.5 microM. On the basis of the data obtained, flavanones and chalcones with isoprenyl groups may be considered as a new class of PTP1B inhibitors.