Drugs with low aqueous solubility not only give low oral bioavailability but provide high inter-and intra-subject variability. Olmesartan medoxomil has very poor aqueous solubility and belongs to Class II drugs under Biopharmaceutical Classification Systems. The purpose of the present study was to investigate the bioavailability enhancement of olmesartan medoxomil by solid lipid nanoparticles. Optimized olmesartan medoxomil loaded solid lipid nanoparticles was prepared by hot homogenization and ultra-sonication method. Optimization was by particle size, polydispersity index, shape and surface morphology determination. Physicochemical and other spectroscopic parameters on optimized formulations (F3 and F7 respectively) were determined. In vitro drug release studies were performed using dialysis bag. Bioavailability studies were done using albino rats. The in vitro drug release study demonstrated that drug-loaded formulations gave higher drug release than olmesartan medoxomil. Zero-order kinetic model best described the release kinetics of the drug from the formulations based on the correlation coefficient values. When compared with the oral tablet of olmesartan medoxomil, the pharmacokinetics of olmesartan medoxomil loaded solid lipid nanoparticles formulations exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability.