Background: Blood-brain barrier (BBB) disruptions are a key feature of hyperglycemia (HG)-induced cerebral damage. Patients with diabetes mellitus often have other cerebrovascular disease risk factors including hypertension, dyslipidemia, arrhythmia, and atherosclerosis obliterans. However, whether the drugs for these comorbidities are effective for improving HG-induced BBB damage is unclear. Methods: We investigated the effect of pitavastatin, candesartan, cilostazol, propranolol, and eicosapentaenoic acid on HG-induced BBB damage. In vitro BBB models consisting of primary cultures of rat brain capillary endothelial cells were subjected to HG (55 mM D-glucose). Results: We observed a significant decrease in transendothelial electrical resistance (TEER) with HG, showing that FIG compromised the integrity of the in vitro BBB model. No significant decrease in cell viability was seen with HG, but HG increased the production of reactive oxygen species. Pitavastatin and candesartan inhibited decreases in TEER induced by HG. Conclusions: In summary, pitavastatin and candesartan improved HG-induced BBB damage and this in vitro model of HG-induced BBB dysfunction contributes to the search for BBB protective drugs. (C) 2018 Elsevier Inc. All rights reserved.