To observe the effect of Met-enkephalin (MENK) on phagocytosis of hemocytes of Oncomelania hupensis, the hemolymph was obtained by squeezing the soft tissues of O. hupensis. The hemocytes in the hemolymph were incubated with different concentrations of MENK (0, 1, 5 and 10 mg/L) in the presence or absence of formaldehyde-treated sheep erythrocyte (FSE) at room temperature for 60 min. The hemocytes were stained with acridine orange and observed under fluorescence microscope. The results showed that the low concentration of MENK (1 mg/L) significantly stimulated the development of pseudopodia in the treated hemocytes of O. hupensis. The rates of pseudopodia development in the group treated with 1 mg/L of MENK was 48.77% (without FSE) and 48.3% (with FSE) with statistical significance compared to the control group (39.99%)(P < 0.01). The low concentration of MENK also stimulated the phagocytosis of treated hemocytes to FSE (48.77%) compared to control group without treatment (40.09%) with significant difference (P < 0.01). However, the high concentration of MENK (5 mg/L or 10 mg/L) not only inhibited hemocytes of Oncomelania to develop pseudopodia [27.04% (5 mg/L), 26.29% (5 mg/L + FSE) , 19.23% (10 mg/L) and 18.3%(10 mg/L + FSE) with significant difference compared to control group(χ² = 99.366, 109.74, 244.446, 274.34, respectively, all P < 0.01), but also dramatically inhibited the phagocytosis rate of treated hemocytes to FSE[7.37% (5 mg/L) and 5.8% (10 mg/L)] compared to 40.09% in untreated control group with statistical significance (P < 0.01). The results demonstrate that low concentrations of MENK can stimulate, but high concentration of MENK can inhibit the phagocytosis of treated hemocytes of O. hupensis.