The purpose of the present study was to improve the bioavailability of buspirone hydrochloride using oil-in-water microemulsion, which was suggested to be suitable for intranasal delivery. Different pseudo-ternary phase diagrams were constructed to determine the microemulsion existing zone. The optimized microemulsion system was chosen. Different formulations were thus prepared and they were subsequently characterized for their polarized light microscopy, % transmittance, droplet size, and pH. An optimal microemulsion formulation consisting of 5% isopropyl myristate, 50% water, and 45% (w/w) surfactant/cosurfactant [Tween 80 30%, propylene glycol 15 % at 2: 1 weight ratio] was transparent with % transmittance 99.52 ± 0.43%, mean globule size 35.1 ± 0.5nm, and pH 6.4 ± 0.03, was thus selected for preparation of buspirone microemulsion formulation. Drug release was carried out using modified Franz diffusion cell. Various pharmacokinetic parameters including C_max, t_max and AUC_0-t were determined using Wister albino rats as the animal model. The absolute bioavailability (0–6 h) was 15.85% compared to the intravenous administration in rats, whereas the oral bioavailability of buspirone hydrochloride was 4%. The results confirmed that the suggested intranasal buspirone microemulsion formulations improved to a much promising extent its bioavailability.