To overcome the side effects of repetitive administration of diazepam (Dzp) besidesgaining benefits from sustaining release of the drug, which contributes to patient compliance,we concentrated on designing and preparing Dzp solid lipid nanoparticles (SLNs). Using cholesterol (CHOL), stearic acid (SA), and glycerol monostearate (GMS), SLNswere prepared by high shear homogenization technique coupled with sonication. Polysorbate80 (Tween 80) was used as a nonionic surfactant. After modification of prepared SLNs, particlesize, zeta potential, drug-loading efficiency, morphology, and scanning calorimetry, as well asrelease studies were conducted. To increase the stability of desired particles, freeze-drying bycryoprotectant was carried out. In the final stage, studies were performed by oral (PO)and intraperitoneal (IP) administrations to Wistar male rats. Results indicated that optimized prepared particles were on average 150 nm diameterin spherical shape with 79.06 % loading efficiency and release of more than 85% of the loadeddrug in 24 hours. investigations also illustrated differences in blood distribution of Dzpafter loading this drug into SLNs. Based on the findings, it seems that drug delivery using SLNs could be anopportunity for solving complications of Dzp therapy in the future.