OBJECTIVE To determine if insulin treatment can enhance the antitumor effect of 5-fluorouracil (5-FU), and to explore the mech-anism of the enhancement of insulin.METHODS $180 sarcoma, H22 liver cancer and human Eca-109 esophageal cancer cells were transplanted into nude mice to evaluate the inhibitory effect on tumor growth of insulin alone or in combination with 5-FU. The levels of serum insulin-like growth factor-Ⅰ (IGF-Ⅰ) and insulin-like growth factor binding protein-3 (IGFBP-3) were determined.RESULTS Compared with 5-FU treatment alone, the tumor weight of H22 liver cancer and $180 sarcoma was reduced further with high, medium and low-dose insulin (0.09, 0.06, 0.03 U/20 g)+ 5-FU treatment. When a high dosage of insulin + 5-FU was ad-ministered, tumor weight was significantly reduced (P < 0.05). The inhibitory rate of growth of S180 sarcoma and H22 liver cancer reached 50.2% and 51.4%, respectively, which was significantly higher than 24.9% and 27.9% in the group receiving 5-FU alone (P