A 30-kDa DBD glycoprotein, which consists of carbohydrate content (61%) and protein content (39%), is a naturally occurring phytoglycoprotein found in Dioscorea batatas Decne (DBD). In the present study, we investigated the anti-inflammatory potentials of the DBD glycoprotein on lipopolysaccharide (LPS, 2 μg/ml)-induced pro-inflammatory signal transduction cascade in murine macrophage cell line (RAW 264.7 cells). Our results showed that the DBD glycoprotein significantly inhibits the translocation of protein kinase C alpha (PKCα) to membrane and the phosphorylation of extracellular signal-regulated kinase (ERK) in LPS-stimulated RAW 264.7 cells. We also found that the DBD glycoprotein (200 μg/ml) has suppressive effects on the DNA binding activities of nuclear factor-kappa B (NF-κB), on the expression of p50, p65, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2, and on the production of superoxide anion radical ( $$ {\text{O}}_{ 2} ^{{ \bullet - }} $$ ) in LPS-stimulated RAW 264.7 cells. Interestingly, the expression of TNF-α and COX-2 was significantly blocked by treatment with PKC inhibitor (Staurosporine) as well as ERK1/2 inhibitors (PD98059). Collectively, we assume that the DBD glycoprotein has anti-inflammatory potential, which can modulate pro-inflammatory signal transduction cascade in LPS-stimulated RAW 264.7 cells.