A 5 yr old male neutered domestic shorthair with intermittent signs of urinary tract obstruction was suspected of having a blood clot in the urinary bladder secondary to trauma. The cat was hospitalized and received standard supportive therapy for urinary tract obstruction with urinary catheterization, with the addition of intravesical saline flushes in an attempt to promote bladder clot lysis. The cat was subsequently discharged after voluntary urination was observed. The cat was represented 28 hr after discharge because of clinical signs consistent with urinary tract obstruction. The cat was hospitalized and intravesical tissue plasminogen activator (tPA) infusions (0.5 mg of tPA in 10 mL of saline with 2 hr dwell time q 8 hr) were administered to break down the bladder clot (2.78 × 4.46 cm). Thirty-two hours after starting tPA, the clot was no longer visible on ultrasound. The cat was discharged with no recurrent symptoms in the subsequent 11 mo. This is the first report of tPA being used for dissolution of bladder clot in a cat. There were no observed complications, suggesting that intravesical instillation of tPA may be a safe and efficacious therapy in cats, similar to the previously reported successes in dogs and humans.