Unlike the nanoparticles with surface plasmon resonance,the optical response of polystyrene nanoparticles (PSNPs) is insensitive to the chemical components of the surrounding medium under the wavelength-dependent differential interference contrast (DIC) microscopy[1,2].This fact is exploited for the measurement of the refractive index of cytoplasm in this study.PSNPs of 400 nm in diameter were loaded into the cell to contact cytoplasm seamlessly,and the refractive index information of cytoplasm could be extracted by DIC microscopy operated at 420 nm illumination wavelength through the contrast analysis of PSNPs images.