Paroxetine (PARX) is the most potent serotonin reuptake blocker antidepressant clinically available. This study is aimed to encapsulation of paroxetine in liposomes and formulation and evaluation of dispersed paroxetine in different gel bases. Paroxetine liposomes were prepared by reverse phase evaporation technique using soya lecithin, cholesterol and drug in different weight ratios. The prepared liposomes were characterized for size, shape, entrapment efficiency. The studies demonstrated successful preparation of paroxetine liposomes. The effect of using different weight ratios of soybean lecithin phosphatidylcholine: cholesterol (SLP: CHOL) on entrapment efficiency and on drug release was studied. Liposomes showed entrapment efficiency percent (% EE) of 81.22% ± 3.08 for paroxetine. The optimized paroxetine liposomes formula was F5 (7:7) molar ratio of (SLP: CHOL), which after that was incorporated in different based gels at different concentrations as Pluronic F127 (PF127-G) (20%, 25%and 30%), Carbopol 934 (C934-G) (1%, 1.5% and 2%) and Hydroxypropyl methylcellulose E4M (HPMC-G) (2%, 4% and 6%) and evaluated through in-vitro release, viscosity, pH and drug content.