Ezetimibe is an anti hyperlipidemic drug which has poor aqueous solubility (0.00846 gm/L) and low bioavailability (35%). The SLNs were prepared using high speed homogenization technique. Glyceryl monostearate (GMS) and Poloxamer 188 were employed as lipid carrier and surfactant respectively. A two factor, three level (32) full factorial design was applied to study the effect of independent variables i.e. amount of GMS (X 1) and amount of Poloxamer 188 (X 2) on dependent variables i.e. Particle size (Y 1 ), % Entrapment efficiency (Y2) and % Cumulative drug release at 24hour (Y3). Particle size, Poly dispersity index (PDI), % Entrapment efficiency (%EE), zeta potential, drug content, in vitro drug release and particles morphology were evaluated for SLNs. Contour plots and response surface plots showed visual representation of relationship between the experimental responses (dependent variables) and the set of input (independent) variables. The optimized batch (B10) contained 500 mg of GMS and 750 mg of Poloxamer 188. Batch B10 exhibited particle size of 38.91±2.23 nm; Polydispersity index (PDI) of 0.221±0.091; zeta potential of -0.623 mV; % EE of 78.1±0.916% and % CDR at 24 hour of102.61±0.927%. The drug release experiments exhibited an initial rapid release experiments exhibited an initial rapid release followed by sustained release extended up to 24 hour. Differential scanning calorimetry (DSC) studies hoed that there was no chemical interaction between drug and lipid. The developed formulation may be adsorbed via the lymphatic route thereby avoiding hepatic first pass metabolism. This may lead to improvement in bioavailability, reduction dose and dose related side effect, etc.