Soluble epoxide hydrolase (sEH) has been proved to be a key enzyme involved in inflammation progression, and inhibition of sEH is therefore very helpful or crucial for the treatment of inflammation-related diseases. In order to uncover new clues suggesting the presence of phytochemical-based sEH inhibitors, and to rationalize the utility of the inflammation-treating Chinese medicinal herbs, the ethanol extracts derived from 46 medicinal herbs, traditionally used for the treatment of inflammation-associated diseases in China, were tested for sEH-inhibition activity using a recently developed sensitive fluorescence-based assay. Screened at 10 microg/mL, four extracts showed substantial inhibitions of sEH (inhibition rates >50%). The ethanol extract of Sophora flavescens root (Fabaceae) possessed the strongest inhibitory activity against sEH (IC(50): 2.07 microg/mL). These preliminary findings highlighted the presence of sEH inhibitor(s) in the plant kingdom, and the possibility that the inflammation-treating herbal medicines could be an untapped reservoir for sEH-inhibition agents.