Lysophosphatidic acid (LPA), a set of bioactive lipid species with simple structure, is able to regulate various cellular activities, and participates in a variety of physiological and pathological processes via binding to the LPA receptors, a series of G protein coupled receptors on cellular membrane. Autotaxin (ATX) is a secretory glycoprotein with lysophosphatidase D (lysoPLD) activity to generate LPA from lysophosphatidylcholine (LPC), which is the main source of circulating LPA. Recently, increasing evidences have revealed that ATX is highly expressed in mature adipocytes and that the ATX-LPA axis plays a role in obesity and obesity-related disorder of glucose and lipid metabolism. The ATX-LPA axis has been regarded as the novel therapeutic target for obesity-related diseases. In the present paper, we will review the research progresses of ATX-LPA axis in obesity and obesity-related diseases, such as insulin resistance and nonalcoholic fatty liver disease.