A Maltese (5-years old, castrated male) and a Yorkshire Terrier (8-years old, intact female) were referred to Seoul National University Hospital for Animals with ataxia, circling, depression and anorexia. It was suspected to meningoencephalitis of unknown etiology (MUE) based on neurological signs, magnetic resonance imaging findings, cerebrospinal fluid analysis and canine distemper virus antigen test. Immunosuppressive dose of corticosteroid was initially chosen to treat in two dogs. However, the clinical signs were relapsed and side effects had arisen including polyuria, polydipsia, calcinosis cutis, liver enzyme elevation, weight gain and abdominal distension. Combination therapy of cytosine arabinoside (CA) and prednisolone (PDS) was tried. With this combination, the clinical signs were resolved and the side effects were alleviated. The dose of PDS was tapered to 0.5 mg/kg q48h in one case and the PDS was discontinued in the other case. These cases suggested that combined CA and PDS therapy may be significantly useful for the treatment of MUE uncontrolled by PDS alone.