Poly(N-isopropylacrylamide-co-acrylic acid) hydrogel submicrometer particles were prepared by free radical copolymerization of N-isopropylacrylamide and acrylic acid in the presence of a crosslinker above the lower critical solution temperature (LCST). They exhibited a reversible swelling and deswelling behavior: ca. 200-nm diameter below the LCST and ca. 100-nm diameter above the LCST The hydrogel particles were tagged with fluorescent dye (FITC) in order to monitor the extent of cellular uptake and were further modified with galactose moieties to evaluate the extent of receptor-mediated endocytosis against HepG2 cells. Flow cytometry and confocal microscopy were used to investigate cellular uptake behaviors of the submicrometer particles. It was found that the extent of cellular uptake of submicrometer particles was far greater above the LCST than below the LCST, suggesting that smaller particles were taken up more readily within cells. When the submicrometer particles were galactosylated, the extent of cellular uptake increased dramatically due to receptor-mediated endocytosis. This study proposes a new possibility of controlling intracellular events such as protein and gene expression by a thermally modulated endocytosis process using thereto-sensitive microgel beads.