Bioassay-guided fractionation of the MeOH extract of the stem bark of Erythrina lysistemon Hutch. resulted in isolation of pterocarpans (1-3), named erylysins A-C, along with nine known pterocarpans (4-12). Their structures were determined to be 3''-hydroxy-2',2'-dimethylpyrano[6',5':3,4]-2'',2''-dimethyldihydropyrano[6'',5'':9,10]pterocarpan (1), furano[5',4':3,4]-9-hydroxy-10-prenylpterocarpan (2), and 8-formyl-3,9-dihydroxy-4,10-diprenylpterocarpan (3), based on spectroscopic analyses. All the isolates, with the exception of 3, 6, and 11, strongly inhibited protein tyrosine phosphatase 1B (PTP1B) activity in an in vitro assay, with IC(50) values ranging from 1.01+/-0.3 to 18.1+/-0.9 microg/mL. This is the first report showing the potential of prenylated pterocarpans as a class of natural PTP1B inhibitors.