The objective of this study was production of nanostructured lipid carriers (NLC) of valproic acid for brain delivery thought the nasal pathway. NLC were prepared by solvent diffusion method using a Taguchi design. The lipid, oil and valproic acid were dissolved in organic phase then dispersed in aqueous phase containing the surfactant. The most effective factors on size were surfactant concentration, organic/aqueous phase ratio and acetone/ethanol volume ratio. Zeta potential was more affected by the lipid type, while the surfactant concentration and sonication time were more effective variables on drug release rate. The entrapment efficiency was more affected by lipid/drug weight ratio. Optimum formulation obtained with 400 mg lipid, 400 mg valproic acid, 2% surfactant, 1:5 organic/aqueous phase ratio, 1:1 acetone/ethanol volume ratio and 2 min sonication.