Thermosensitive gels have been developed and optimized in such a way that they become gels at corneal temperature and with a viscosity that allows the adequate release of the Fluorometholone (FMT)-loaded PLGA nanoparticles (NPs) in order to improve ocular anti-inflammatory efficacy against a commercial formulation. It has been shown that gels avoid burst release of the drug in the first hours with a slow and increasing profile after administration. NPs have maintained their average size and spherical shape within the gels as confirmed by transmission electron microscopy (TEM). In turn, the in-situ gelling of the formulations allows the administration in eye drops dosage form due to its state of sol at temperatures below 25 °C. Ocular tolerance studies have shown that no formulation causes eye irritation. The administration of the developed formulations has improved the precorneal residence time reflected in the ocular bioavailability, where deep tissues as aqueous humour and crystalline were reached. In conclusion, the use of thermosensitive gels for the topical application of NPs has demonstrated their effectiveness in the acute and preventive treatment of ocular inflammatory conditions.