Dioscorea is a traditional medicinal food in Asia. This study investigated the anti-insulin resistance of dioscorea polysaccharide (DPS) in inflammatory factor (tumor necrosis factor-α; TNF-α) induced mouse normal liver FL83B cells. Insulin resistance was induced by treating cells with TNF-α (20 ng/mL) for 5 h; subsequently, the medium was replaced with insulin and DPS for 60 min of incubation (model 1; alleviating group). In addition, cells were cotreated with TNF-α and DPS for 5 h in model 2 (preventing group). DPS effectively increased glucose uptake and glucose transporter 2 (GLUT2) expression of insulin-resistant cells. Furthermore, DPS stimulated insulin receptor substrate (IRS) tyrosyl phosphorylation and increased p-Akt level to alleviate insulin resistance in models 1 and 2. Finally, the possible mechanism of DPS promoting insulin sensitivity in TNF-α-induced FL83B cells was investigated in this study. DPS may attenuate c-Jun N-terminal kinases (JNK) and insulin resistance caused by TNF-α induction; therefore, DPS also elevated the levels of p-IRS(Tyr) and p-Akt(Ser) to improve insulin sensitivity in the TNF-α-induced FL83B cells.