Salvia plebeia R.Br. (SPRB) is a natural resource that exhibits various biological activities. However, its effects on inflammatory diseases are not yet well characterized. This study aimed to evaluate the inhibitory effects of a compound derived from SPRB on interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) activation. The chemical structure of active compounds isolated from the EtOAc-soluble fraction of SPRB were elucidated by comparison with spectroscopic nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI MS) data in the literature, which resulted in the identification of 22 known compounds. All of the isolated compounds were evaluated for potentially higher inhibitory effects on IL-6-induced STAT3 activation in Flep3B cells using a luciferase reporter assay. Furthermore, the protein levels of p-STAT3, p-ERK, and p-JAK2 in IL-6 induced U266 cells were regulated in the presence of cirsimaritin from SPRB by western blot assay. Based on these findings, we suggest that SPRB has the potential to inhibit IL-6-induced STAT3 activation and should be considered in functional food and pharmaceutical applications. (C) 2016 Elsevier Ltd. All rights reserved.