The objective of this study is to explore the influence of polyvinylpyrrolidone (PVP) quantity on the solubility, crystallinity and oral bioavailability of poorly water-soluble fenofibrate in solvent-evaporated microspheres. Numerous microspheres were prepared with fenofibrate, sodium lauryl sulphate (SLS) and PVP using the spray-drying technique. Their aqueous solubility, dissolution, physicochemical properties and pharmacokinetics in rats were assessed. The drug in the solvent-evaporated microspheres composed of fenofibrate, PVP and SLS at the weight ratio of 1:0.5:0.25 was not entirely changed to the amorphous form and partially in the microcrystalline state. However, the microspheres at the weight ratio of 1:4:0.25 provided the entire conversion to the amorphous form. The latter microspheres, with an improvement of about 115000-fold in aqueous solubility and 5.6-fold improvement in oral bioavailability compared with the drug powder, gave higher aqueous solubility and oral bioavailability compared with the former. Thus, PVP quantity played an important role in these properties of fenofibrate in the solvent-evaporated microspheres.