We investigated the proteins showing differential expression in response to $TiO_2$ nanoparticles in mouse kidney using a proteomic approach to better understand the molecular mechanism by which $TiO_2$ nanoparticles-induced nephrotoxicity at the protein level. More than 1,100 protein spots in mouse kidney were detected by the two-dimensional gel eletrophoresis and comparative analysis revealed that the expression of 11 proteins were changed by more than 2 fold in response to $TiO_2$ nanoparticles. Of these, 10 were up-regulated and 1 was down-regulated upon treatment with $TiO_2$ nanoparticles.