To investigate the anti-inflammatory impacts of piroxicam nanosuspension, in the current investigation, piroxicam:Eudragit RS100 nanoformulations were used to control inflammatory symptoms in the rabbits with endotoxin-induced uveitis (EIU). The nanoparticles of piroxicam:Eudragit RS100 was formulated using the solvent evaporation/extraction technique. The morphological and physicochemical characteristics of nanoparticles were studied using particle size analysis, X-ray crystallography, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Drug release profiles were examined by fitting the data to the most common kinetic models. Selected nanosuspensions were used to assess the anti-inflammatory impacts of piroxicam nanoparticles in the rabbits with EIU. The major symptoms of EIU (i.e. inflammation and leukocytes numbers in the aqueous humor) were examined. All the prepared piroxicam formulations using Eudragit RS100 resulted in a nano-range size particles and displayed spherical smooth morphology with positively charged surface, however, the formulated particles of drug alone using same methodology failed to manifest such characteristics. The Eudragit RS100 containing nanoparticles displayed lower crystallinity than piroxicam with no chemical interactions between the drug and polymer molecules. Kinetically, the release profiles of piroxicam from nanoparticles appeared to fit best with the Weibull model and diffusion was the superior phenomenon. The in vivo examinations revealed that the inflammation can be inhibited by the drug:polymer nanosuspension more significantly than the microsuspension of drug alone in the rabbits with EIU. Upon these findings, we propose that the piroxicam:Eudragit RS100 nanosuspensions may be considered as an improved ocular delivery system for locally inhibition of inflammation.