Purpose: Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still suffer from seizures and/or drug related cerebral and systemic side effects. Local intracerebral delivery of anti-epileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the anti-epileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods: Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG. Seizures were scored during two weeks of local hippocampal delivery of saline (baseline), followed by two weeks of local adenosine (6mg/ml) (n=10) or saline (n=5) delivery (0.23µl/h) (treatment). In 7/10 adenosine-treated rats, saline was also delivered during a washout period. Results: During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine-treated rats (p