Background: Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases;however, the scientific basis for such usage and the mechanism of action are not well understood. This studyinvestigated the action of M. alba on leukocyte migration, one key step in inflammation.Methods: Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extractsof three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry andCXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. albaand its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses wereconducted to determine the mode of action of oxyresveratrol.Results: Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identifiedoxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crudeextract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in responseto SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibitionof the MEK/ERK signaling cascade.Conclusions: A combination of GC-MS and cluster analysis techniques are applicable for authentication of theMorus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve theinhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells