The use of liquid crystalline nanoparticles is a novel approach in the field of controlled drug delivery. Tacrolimus, being a highly lipophilic drug, is easily incorporated in the hydrophobic core of these nanoparticles. Which are prepare by pseudo binary mixture technique by using polymers like monoolein and poloxomer 407 to extend the drug release for about 32 hours, there by improved bioavailability. Formulation optimization of tacrolimus loaded liquid crystalline nanoparticles was carried out by using different concentration of monoolein and poloxomer 407. Total 10 batches were formulated. The process optimization was carried out at three different stirring speeds i.e. 2200, 2500 and 2800 rpm for three different stirring time period i.e. 05mins, 10mins and 15mins. Out of all the batches S5 showed the spherical shape of liquid crystalline nanoparticles. All 10 batches were evaluated for entrapment efficiency (EE) and particle size (nm). Among all batches S5 shows maximum entrapment efficiency (EE) and uniform particle size and was considered as optimized formulation. Optimized batch S5 was evaluated for Zeta Potential, Particle Size Distribution which show -35.4mV and 126.1nm particle size, TEM Analysis. Batch S5 was charged for stability and were placed in glass vials container and stored at ICH storage condition (30 ± 2°C / 60% ± 5% RH , 40 ± 2°C / 75% ± 5% RH ) for a period of 30 days. The samples were analyzed for physical appearance, entrapment efficiency and particle size after 30 days. After 1 months samples were withdrawn and liquid crystalline nanoparticles showed no change in physical appearances, entrapment efficiency and particle size, which indicate that the liquid crystalline nanoparticles were stable. Therefore, study suggests the possible use of tacrolimus-loaded formulation for intradermal or topically delivery can be useful in the treatment of locally affecting autoimmune skin disease such as psoriasis.