Hyaluronic acid(HA)is one of the main components of the extracellular matrix(ECM), and it is participated in many cells physiology and pathological processes, such as tissue reconstruction, expansion of cell gap, inflammation and tumorigenesis and so on. CD44 is a cell surface receptor for HA and widely distributed cell surface glycoprotein, which paticipate in specific adhesion of cell to cell and cell to matrix. CD44 is the most important hyaluronic acid receptor on the cell surface. Besides, CD44 is the main site of binding to HA. In this paper, we will elaborate from three aspects: the binding of HA and CD44 and its molecular basis, the expression and significance of HA/CD44 in glial cells(including Müller cells)and the expression and significance of HA/CD44 in the optic nerve, which makes readers have an understanding of the role of HA and CD44.