AbstractAims: To determine whether the blood–brain barrier (BBB) opens to enhance drug delivery during the acute stage of unsaturated fat embolism.Methods: We infused oleic, linoleic, and linolenic acid emulsions through the right common carotid artery of rats, followed by trypan blue for gross and lanthanum for electron microscopic (EM) examination. Doxorubicin and temozolomide were also administered, and then the rats were euthanized at 30 min, 1 h, and 2 h. Trypan blue hue was analyzed to semiquantitatively measure BBB opening. Desorption electrospray ionization–mass spectrometry (DESI–MS) imaging was used to evaluate drug delivery.ResultsTrypan blue staining observed in each group 30 min after emulsion infusion increased at 1 h and decreased after 2 h in the oleic acid group. The linoleic and linolenic acid groups showed weak staining over time. The hue and trypan blue analysis results were corroborative. EM showed tight junction opening, whereas DESI–MS imaging showed increased doxorubicin and temozolomide signal intensities in ipsilateral hemispheres of all three groups.ConclusionWe demonstrated that oleic, linoleic, and linolenic acid emulsions opened the BBB, promoting drug delivery to the brain. Hue analysis and DESI–MS imaging are appropriate for analysis of doxorubicin and temozolomide concentrations in brain tissue.