The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue. The protein levels of Toll-like receptor 4 (TLR4) were also downregulated by EDH-1e and EDH-2b treatment as were the levels of activator protein 1 (AP-1), c-fos, and c-jun in the livers from Western-type diet-fed ApoE (-/-) mice and in lipopolysaccharide-stimulated HepG2 cells. Taken together, EDH-1e and EDH-2b attenuated hepatic inflammation and fibrosis via suppression of the TLR4-AP1-mediated signaling pathway.