A rodent model was used to study tissue expansion. Three chemical agents—hyaluronidase, prostaglandin E2, and colchicine—were administered and their effects on tissue expansion studied. Hyaluronidase and colchicine both enhanced the rate of expansion when compared with results in control animals (p < 0.05). Although prostaglandin E2had less effect on expansion rate, it did significantly enhance tissue oxygen tension of expanded skin when compared with controls (p < 0.05). Clinical implications include the possibility of pretreating patients with these agents to increase the rate of expansion and to improve the safety of current methods of expansion.