Triggering changes in surface porosity enabled the controlled release of biomolecules from elastin-like polypeptide (ELP) microspheres. The transition temperature (T(t)) of cross-linked microspheres was determined by differential scanning calorimetry, and T(t) was in agreement with the volume transition observed by changing the external temperature of the incubation media. The thermoresponsive pore structure of ELP microspheres and their surface morphology were examined by field-emission scanning electron microscopy. ELP microspheres were investigated as a smart drug carrier using model drug molecules, bovine serum albumin, and prednisone acetate. The release rate was accelerated by squeezing out the entrapped biomolecules as the temperature was increased above T(t) because of the development of micropores at the surface as well as in the bulk. In addition, the stepwise release confirmed that ELP microspheres could be progammed precisely to control the release of drugs by external stimuli.