Recent studies showed that the activation of toll-like receptor 4 (TLR4) on dorsal root ganglion (DRG) neurons might underlie neuropathic and inflammatory pain states. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties on the inflammatory reaction and TLR4 dependent pathways in lipopolysaccharide (LPS)-treated DRG neurons. Our results showed that wogonin not only inhibited the expression and interaction of TLR4, MyD88, and TAK1, but also reduced the activation of nuclear factor kappa B and mitogen-activated protein kinases pathway in LPS-treated DRG neurons. Moreover, wogonin significantly suppressed the release of pro-inflammatory mediators in LPS-induced DRG neurons, including cyclooxygenase-2, inducible nitric oxide synthases, interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha. Our results suggested that pre-treatment with wogonin could attenuate the TLR4-mediated inflammatory response in LPS-induced DRG neurons, thus might be beneficial for the treatment of neuropathic and inflammatory pain.