The aim of present study was to develop and evaluate in-situ ophthalmic gel system based on sol-to-gel transition for concomitant delivery of ofloxacin (OFL) and diclofenac sodium (DS) to facilitate sustained release to improveocular bioavailability and therapeutic response exhibited by conventional formulations.A 32 full factorial design was adopted to optimize the experimental conditions for development of formulation using Carbopol 940 and HPMC as independent variable. Developed formulations were characterized in terms of physical appearance, pH, viscosity, drug content, gelling capacity, and in-vitro drug release. Further, ex-vivo permeation and in-vivo irritation studies were conducted. The pH, viscosity and drug content of all developed formulations were found in the range of 5.2±0.02-6.5±0.04, 12±1.26-114±2.05cps and 88.32±2.26-98.46±1.36% respectively. The gel provided sustained drug release over an 8 h period. Furthermore, in-vivo ocular irritation study and antimicrobial efficiency of optimized formulation suggest that developed formulation was therapeutically efficacious and non-irritant. In conclusion, developed in-situ gelling system would be used to enhance ocular bioavailability of the loaded drugs and could reduce the frequency of instillation thereby improving patient compliance.