Abstract: High concentration insulin was added into HepG2 cells to induce glucose metabolism abnormal.The optimal conditions of insulin resistant HepG2 cells ( HepG2 /IR) model was investigated from insulin dose and effect time.HepG2 cells were divided into control group, insulin resistant group, pioglitazone hydrochloride group, bitter melon saponin groups ( 100, 300, 500, 700μg /mL) . The glucose consumption was measured by glucose oxidase method ( GOD) .The cell activity was estimated by MTT method.These results showed that treatment with 30μg /mL insulin for 36h was the best condition for induction of HepG2 /IR model.Compared with HepG2 /IR group, treatment with 300μg /mL bitter melon saponin not only could alleviate insulin resistant HepG2 cells significantly, but cell activity was increased.