Autotaxin (ATX) hydrolyzes lysophosphatidylcholine to produce lysophosphatidic acid (LPA), a multi-functional bioactive lipid mediator. ATX is a major determinant of LPA levels in the blood, and the pathophysiological functions of ATX are thought to be largely attributed to its ability to produce LPA. Liver fibrosis is one of the rare disorders exhibiting the increased ATX and LPA levels in the blood. This review summarizes the recent findings on the relation between ATX or LPA and liver fibrosis, the usefulness of serum ATX levels to predict the stages of liver fibrosis, and speculated roles of increased serum ATX and plasma LPA levels in liver fibrosis.