Potential positive effects of flavonol quercetin on humans were suggested by many studies. However, it is not clear if these effects are mediated by quercetin or its metabolites. The in vivo confirmation of quercetin effects is largely hindered by its low water solubility and thus impossibility to test directly its impact. Therefore, a solid dispersion of quercetin with polyvinylpyrrolidone (PVP) was developed to prepare an injectable formulation of water-soluble quercetin. The optimized formulation provided a 20,000-fold increase in quercetin solubility. This formulation was tested on conventional and spontaneously hypertensive rats; it lowered their blood pressure in both short- and long-term basis. Pharmacokinetic data are also provided. This study reports for the first time an injectable water-soluble formulation of quercetin suitable for confirmation of its vascular effect in vivo.