Current therapies for epilepsy consist mostly of pharmacological agents or invasive surgery. Recently, ultrasound (US) stimulation has been considered a promising tool for the noninvasive treatment of brain diseases, including epilepsy. However, in temporal lobe epilepsy (TLE), a common form of epilepsy, neurophysiological and functional outcomes following US stimulation are not well defined. To address this we developed a paradigm of transcranial pulsed US stimulation to efficiently suppress seizure activity in the initial acute period in a kainate (KA)-inducecl mouse model of mesial TLE. Pulsed US stimulation inhibited acute seizure activity and either delayed! the onset of or suppressed status epilepticus (SE). Kainate-treated mice that had received US stimulation in the initial period exhibited fewer spontaneous recurrent seizures (SRSs) and improved performance in behavioral tasks assessing sociability and depression in the chronic period of epilepsy. Our results demonstrate that US stimulation in the acute period of epilepsy can inhibit SRSs and improve behavioral outcomes in a mouse model of menial TLE. The present study suggests that noninvasive transcranial pulsed US stimulation may be feasible as an adjuvant therapy in patients with epilepsy. This article is part of a Special Issue entitled "Status Epilepticus".