Drug eluting vascular closure devices and methods for closing a blood vessel puncture site disposed at a distal end of a tissue tract are described. The devices and methods rely on a combination of the body's own natural mechanism to achieve hemostasis with chemical and/or biological agents to accelerate the hemostatic process. One method includes the steps of introducing a closure device through the tissue tract and deploying an expansible member at a distal end of the device within the blood vessel to occlude the puncture site. A chemical and/or biological sealing member disposed proximal the expansible member is then displaced so as to expose a chemical and/or biological region or release region of the device. At least one chemical and/or biological agent is thereafter released from the device and into the tissue tract to accelerate the occlusion process in the tract.