In order to investigate the inhibitory eff ects of oyster enzymatic hydrolysate (OEH) on the metastasis of Lewis lung cancer and to evaluate its mechanism, daily gavage of low(LOEH), medium(MOEH) and high (HOEH) doses of OEH for 5 weeks was administered based on the subcutaneous Lewis lung cancer model in C57BL/6J male mice, the volume and weight of subcutaneous tumor were measured, the lung metastatic nodules were counted, the number of tumor-associated-macrophages (TAMs; CD11b+F4/80+), the expression of E-cadherin, Vimentin, microRNA-21 and microRNA-218 in subcutaneous tumor were measured. It was found that OEH treatment significantly decreased the subcutaneous tumor weight for the MOEH and HOEH groups (P=0.013, P=0.007) and significantly inhibited lung metastasis in a dose-dependent manner (χ2=13.16, P=0.004). The expression of E-cadherin showed a statistical increase at high dose, while the expression of Vimentin and the number of TAMs in subcutaneous tumor was significantly decreased at all OEH doses (P