**Abstract**

Increasing evidence implicates the enzyme Heparanase in the development and progression of liver steatosis and fibrosis, where high heparanase expression was demonstrated. Morever, inhibition of heparanase activity significantly attenuated the development of fatty liver in animal models. Non-alcoholic fatty liver disease is the most common liver disease in the western world, with the natural course of a chronic progressive condition that is expected to worsen with time. Potential complications of the disease are steatohepatitis, liver fibrosis, liver cirrhosis and even liver malignancies, such as hepato-cellular carcinoma. As such, non-alcoholic fatty liver disease is considered a leading etiology for liver transplantation in the western world. No effective treatment for fatty liver is available so far, and seeking effective treatment strategies is of great importance. The aim of this chapter is to shed light on the knowledge regarding the involvement of Heparanase in the development and progression of fatty liver, opening the opportunity for future research of potential therapeutic options for treating this common liver pathology.

**Keywords:** Heparanase, lipid uptake, liver steatosis, fatty liver, inflammation, extracellular matrix
