Oral in situ gelling systems provide many advantages over the conventional oral dosage forms in various aspects. In situ gels undergo transformation from solution to gel like consistency, due to change in their physicochemical properties. In situ gels also combines the advantages of both gels and solutions by providing environment specific gel forming solution and capable of producing the sustained and controlled drug delivery. Pluronic F-127 is a thermoresponsive polymer that exists in a liquidstate at low temperature, while converting into a gel upon increasing the temperature of the medium. It is a non-ionic and amphiphilic polymer, while being the least toxic and most commonly used thermosensitive polymer in pharmaceutical formulations. In this study, ketorolac tromethamine (KT), a non-steroidal inti-inflammatory drug with a short plasma life approximately 5.5 h, was loaded into Eudragit RS 100 nanoparticles produced by the spray-drying method. KT loaded nanoparticles implemented in the Pluronic F-127 based in situ gelling system for controlled released oral delivery. Characterization of the nanoparticles and gel system was conducted, and the safety of the novel drug delivery system was evaluated by the MTT assay. The nanoparticle loaded in situ gel system found to be safe and promising for oral delivery of ketorolac tromethamine.