Autotaxin (ATX) catalyzes the hydrolysis of lysophosphatidylcholine (LPC) generating the lipid mediator lysophosphatidic acid (LPA). Both ATX and LPA are involved in various pathological inflammatory conditions, including fibrosis and cancer, and have attracted great interest as medicinal targets over the past decade. Thus, the development of novel potent ATX inhibitors is of great importance. We have developed a novel class of ATX inhibitors containing the zinc binding functionality of hydroxamic acid. Such novel hydroxamic acids that incorporate a non-natural δ-amino acid residue exhibit high in vitro inhibitory potency over ATX (IC50 values 50-60 nM). Inhibitor 32, based on δ-norleucine, was tested for its efficacy in a mouse model of pulmonary inflammation and fibrosis induced by bleomycin and exhibited promising efficacy. The novel hydroxamic ATX inhibitors provide excellent tools for the study of the role of the enzyme and could contribute to the development of novel therapeutic agents for the treatment of fibrosis and other chronic inflammatory diseases.