The drug development for regulating the excess innate immune reactions is important to prevent inflammatory diseases. Resveratrol is a structural unit of its oligomers and has various neuroprotective effects such as the inhibition of chemokine expression. The aim of our study is to investigate the effects of resveratrol oligomers on CXCL10 expression, a chemoattractant of lymphocytes into brain. We examined the effects of (+)-hopeaphenol, a resveratrol tetramer, and its derivatives on CXCL10 expression induced by polyinosinic–polycytidylic acid (poly IC; a synthetic analog of dsRNA as a Toll-like receptor 3 ligand) in cultured human cerebral microvascular endothelial cell line. Only (+)-hopeaphenol (1-10 μM) inhibited poly IC-induced CXCL10 expression in a dose-dependent manner. We further confirmed that (+)-hopeaphenol significantly reduced poly IC-induced expression of IFN-β, an upregulator of CXCL10. Phosphorylation of NF-ĸB, but not of interferon regulatory factor 3, was inhibited by (+)-hopeaphenol. These results suggest that (+)-hopeaphenol can negatively regulates poly IC-induced NF-ĸB/IFN-β/CXCL10 axis, and may be effective to prevent inflammatory diseases associated with excess innate immunity.