Eosinophilic cystitis is a rare and poorly understood disorder. We report the first case of an acute flare of eosinophilic cystitis in a 51-year-old woman after bladder instillation with dimethyl sulfoxide (DMSO) for presumed interstitial cystitis. The patient presented with severe bladder pain, fever, and eosinophilia several hours after instillation. These symptoms were unresponsive to conventional analgesic and antibiotic treatments. Cystoscopy revealed erythema and exudate at the bladder walls, along with edema of both ureteral orifices. Bladder biopsies demonstrated massive eosinophilic infiltration of the bladder, confirming the diagnosis of eosinophilic cystitis. Urologists should bear in mind this clinical entity, particularly when DMSO is administered to patients with multiple drug allergies.