The hyaluronidase-mediated degradation of hyaluronic acid to hyaluronic acid oligosaccharides was investigated. The final products of the batch reaction were the tetrasaccharide and hexasaccharide only. In the reaction solution containing an inorganic salt such as NaCl, the yield of hexasaccharide was higher than that of tetrasaccharide. However, in the absence of inorganic salt, the tetrasaccharide was generated preferentially. The yield of each oligosaccharide depended on the nature of the inorganic salt used. In the batch reaction, the product yield was approximately 60%. However, a continuous reaction increased the yield to about 85% within the first 200 h of operation.