A 4-year-old, female, Maltese dog with bilateral hind limb ataxia was brought to Gyeongsang National University Animal Medical Center (GAMC). Based on the previous medical and imaging records, the patient was presumptively diagnosed with a primary brain tumor of the right temporo-occipital lobe on magnetic resonance imaging (MRI) in a local animal hospital. Hydroxyurea and prednisolone therapy was initiated, and the neurological signs transiently improved. Approximately 5 months after the treatment, ataxia recurred and the patient was referred to GAMC. Upon admission, MRI at the same anatomic level as in the previous MRI was performed. Results showed inflammatory brain lesions, not brain neoplastic changes. Considering this finding, the dog was tentatively diagnosed with meningoencephalitis of unknown etiology (MUE). We added oral imatinib mesylate (10 mg/kg every 24 h), and the dosage of prednisolone was increased to 1 mg/kg twice daily. Hydroxyurea was discontinued. A rapid improvement in neurological signs was observed after the initiation of imatinib mesylate treatment. Approximately 2 months after the treatment, the size of the inflammatory lesion remarkably decreased on repeat MRI. The patient had been doing well, and there were no overt neurological signs 259 days after the initiation of imatinib mesylate therapy. We describe a case of MUE in a dog that was successfully managed with imatinib mesylate.