The hyaluronidases are a family of enzymes that degrade hyaluronic acid.

By catalyzing the hydrolysis of hyaluronic acid, a major constituent of the interstitial barrier, hyaluronidase lowers the viscosity of hyaluronic acid, thereby increasing tissue permeability. It is, therefore, used in medicine in conjunction with other drugs in order to speed their dispersion and delivery. The most common application is in ophthalmic surgery, in which it is used in combination with local anesthetics. It also increases the absorption rate of parenteral fluids given by hypodermoclysis, and is an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Hyalurodinase is also used for extravastation of hyperosmolar solutions. usually a 0.2 ml of the drug is injected around the area of extravastation, Total of 1 ml is used.

Some bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Clostridium perfringens, produce hyaluronidase as a means for greater mobility through the body's tissues and as an antigenic disguise that prevents their being recognized by phagocytes of the immune system.

In most mammalian fertilization, hyaluronidase is released by the acrosome of the sperm cell after it has reached the oocyte, by digesting proteins in the zona pellucida, thus enabling conception.

Brand names of animal-derived hyaluronidase include Vitrase (ISTA Pharmaceuticals), Amphadase (Amphastar Pharmaceuticals) and Wydase. Wydase, however, is no longer manufactured. On December 2, 2005, the FDA approved a recombinant hyaluronidase, Hylenex (Halozyme Therapeutics).