The delivery of drugs to the brain is a constant challenge due to limitations imposed by the blood-brain barrier (BBB). Various methods of bypassing the BBB are under investigation. One approach is intranasal administration, where the olfactory region of the nasal cavity extends up to the cranial cavity and provides direct access to the brain. The pharmacokinetics of this transport and factors that determine transport rates and capacity is of vital importance for evaluating the clinical value of this route. Here, the pharmacokinetics of intranasally administered imatinib has been explored. Imatinib is distributed into the brain following intravenous administration, and then rapidly removed. Following intravenous administration, the brain/plasma ratio for imatinib was calculated to be 2% and remained at this ratio for 30min. The brain/plasma ratio following intranasal administration, however, was found to be 5.3% and remained at this ratio for up to 90min. Imatinib was found to be rapidly transported into the brain via the olfactory region, by shutting down the nose-to-blood-to-brain transport with epinephrine. The increased brain concentration of imatinib (0.33μg/g tissue) achieved by intranasal administration, compared with an IV injection, is likely to provide a model for developing a wide range of CNS active molecules that were previously removed from consideration as drug candidates due to their lack of CNS access. Furthermore, brain imatinib levels were increased by co-administration of the p-gp substrates, elacridar and pantoprazole, showing that both compounds were able to inhibit the elimination of imatinib from the brain.