In partial epilepsies focal onset of seizures arise from specific regions and spread across the brain. The underlying cellular mechanism is unclear and it may involve astrocytes. Indeed, these glial cells respond to most neurotransmitters with Ca²⁺ elevations and affect neuronal activity by releasing gliotransmitters such as glutamate, ATP and D-serine. Using confocal fast laser scanning microscopy and simultaneous patch-clamp recordings we studied the astrocyte contribution to focal ictal discharges (IDs) generation and propagation in two experimental slice models. In the first, spontaneous IDs arising at unknown sites upon slice perfusion with low Mg²⁺ and picrotoxin were observed to strongly activate astrocytes. Blockade of mGlu or purinergic P2Y receptors reduced significantly astrocytic activation as well as ID duration and frequency. In the second, we used a new model that allows to trigger reproducible IDs from a restricted focal site (Losi et al. 2010) and found that at this site, astrocyte activation precedes and favors ID generation. BAPTA introduced into patched astrocytes or mGluR/P2Y receptor antagonist local applications impaired both astrocyte activation and ID generation at the focal site. Distant from the focus, a strong powerful GABAergic inhibition transiently opposes ID propagation. This action of interneurons is accompanied by Ca²⁺ elevations in a number of astrocytes mediated by GABA_B receptor activation. These latter observations suggest that GABA signaling to astrocytes may play a role in the control of ID propagation. Altogether our data hint at a distinct role of gliotransmission during both seizure generation and propagation.