It has been reported that endogenous opioid system including enkephalin exists in mollusk and other invertebrates and plays an important role in their physiological and biochemical such as growth and reproduction. This review updates the research findings about enkephalin in mollusk and other invertebrates, including its location,isolation and identification, as well as its related enzymes. The functional and mechanistic research of the enkephalin in invertebrates is still at a preliminary stage and needs to be further explored.