Poly lactic-co-glycolic acid (PLGA) is biodegraded mainly through hydrolysis of its ester linkages, self-catalysis, or phagocytosis by macrophage. Lactic acid and glycolic acid, the products of hydrolysis process, are then eventually catabolized into carbon dioxide and water which are eliminated via lungs and kidneys, respectively. Only trace PLGA is excreted in urine. No accumulation of PLGA is found in the body. PLGA showed excellent biocompatibility and biodegradability, so it is safe for using as materials for scaffolds of tissue engineering and drug controlled release system, and the US Food and Drug Administration (FDA) has approved its use for preparation of scaffolds for tissue engineering and carrier of drug. It has been used in the market in United States and Japan for many years, and no serious side effects have been reported. At present, the quality of domestic PLGA and the development of drug controlled release system with this material still need improving, especially amount of drug loading, release controling, and stability of the preparation. This paper describes recent advances in the studies on biodegradation and safety of PLGA, which will provide the reference for the development of PLGA controlled release system.