Purpose: The objective of this study was to develop, characterize, and comparatively investigate the ketotifen fumarate (KF) nanosuspensions (NSS) to enhance the permeability of KF.Methods: In the present work, the NSP and NSE were prepared by double-emulsion solvent evaporation/nanoprecipitation methods with poly (D, Llactide-co-glycolide) and Eudragit RL100 polymers, respectively. The loading efficiency, particle size, and polydispersity index of prepared different NSs were evaluated with scanning electron microscopy (SEM), X-ray diffraction, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and in vitro release and transcorneal permeation. NSs were also compared on the basis of particle size and polydispersity index.Results: Particle size, polydispersity index, and loading efficiency of NSP1 and NSE3 showed the best value (158 nm, 117 nm, 0.21, 0.43 and 43%, 95.23%, respectively). SEM showed spherical globules and DSC results showed the reduction in crystallinity. The NSE3 formulations demonstrated significantly (p<0.05) higher drug release rates than the NSP1 due to increases in the surface area. Comparative studies showed that NSE release and permeability are higher than NSP.Conclusion: It is concluded that both NSP and NSE provide a useful dosage form for the ocular drug delivery which can enhance the permeability of KF.