The aim of this work is to formulate topically effective controlled release ophthalmic liposomal gel for targeting diclofenac sodium to the eye in an attempt to heal the inflamed tissue of ocular ulcerative area. Large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs) gel formulations composing of phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (7:2; 7:4 and 7:7) with or without stearylamine (SA) or dicetylphosphate (DP) were prepared using reversed-phase evaporation and lipid film hydration methods respectively. The prepared liposomal systems were evaluated for their entrapment efficiency, morphological characters, physical stability, particle size and drug release rate .LUVs entrapped greater amount of drug than MLVs. Drug loading was increased by increasing CH content as well as by inclusion of SA into the lipid bilayer. Drug release rate showed an order of negatively > neutral > positively charged liposomes, which is the reverse of results of drug loading efficiency. Physical stability study indicated that 92.56%, 84.11%, 76.41% and 91.1%, 82.19% and 75.54% of diclofenac sodium was retained in positive, negative, and neutral MLVs and LUVs respectively after storing for 120 days at refrigeration temperature. The in vivo anti-inflammatory activity was evaluated using a thermal technique , results showed that the percentage of healed ulcers were 12.5%, 35%, 67.5%, 82.5%, 85%, 87.5% and 95% for negative control, positive control, 0.5% carbopol 934 gel, LUVs liposomes suspension, MLVs liposomes suspension, LUVs and MLVs gels, respectively.