Inflammation in the retinal pigment epithelium is an important contributor to the pathogenesis of age-related macular degeneration. Wogonin is a flavonoid isolated from the root of Scutellaria baicalensis and has multiple pharmacological effects, including anti-inflammatory effects. The present study sought to determine if the pharmacological effects of wogonin were relevant to the treatment of AMD. ARPE-19 cells were pre-conditioned with different concentrations of wogonin (0-50 mu M) prior to induction of inflammation with LPS (2 mu g/ml). Transepithelial electrical resistance analysis demonstrated that 24 h treatment with 10 and 50 mu M wogonin ameliorated LPS-induced changes. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence analyses revealed that wogonin restrained LPS-induced tight junction proteins, claudin-1 and ZO-1. LPS-induced upregulation of inflammatory mediators in ARPE-19 cells, including IL-1 beta, IL,-6, IL,-8, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and TNF-alpha was reduced after pre-treatment with wogonin. In addition, RT-qPCR and western blotting demonstrated that wogonin inhibited the expression of TLR4 in LPS-stimulated ARPE-19 cells. This is a novel mechanism indicating that pre-treatment with wogonin could attenuate the TLR4/NF-kappa B-mediated inflammatory response in LPS-stimulated ARPE-19 cells, and thus could be a potential therapy for the treatment of AMD.