The permeability of microspheres in normal round window membrane was studied in guinea pigs under the transmission electron microscopy. Latex microsphere suspensions with each sizes of 3, 1, 0.5, 0.1μm were instilled into the middle ear cavity for each durations of 30 minutes, 3 hours, or 24 hours. The microspheres of 3μm and 1μm were attached on the middle ear surface of the epithelial cell, and were not penetrated into the cytoplasm of the epithelial cell. The microspheres of 0.5μm and 0.1μm were found in the cytoplasm of the epithelial cell, and were not found in the middle layer and inner layer. The mode of microsphere uptake of the epithelial cell was accomplished by pinocytosis. First, latex microspheres adhered to the surface of the epithelial cell ; then the cytoplasm invaginated to form a vesicle containing these microspheres, and the vesicle was pinched off into the cytoplasm of the epithelial cell. In the membranous endocytic vesicle microspheres were aggregated with electron dense matrix. No penetration of the epithelial intercellular tight junction was found. The polymorphonuclear leukocytes infiltrated into the middle layer of the round window membrane, and those were also found in the middle ear cavity.