Introduction: Epileptogenesis is the molecular and cellular process by which a healthy brain becomes an epileptic one. Some evidence suggests that the disruption of circadian rhythms may be impacting the epilepsy phenotype. However, whether the molecular clock is a key player in epileptogenesis remains to be elucidated. Here, we mapped for the first-time the hippocampal molecular rhythmicity of mice during epileptogenesis. Methods: Male adult C57BL/6 mice (n=5/group/Zeitgeber-Times [ZTs]) underwent intra-amygdala kainic acid-induced (i.a.KA) status epilepticus or control (i.a.PBS). From 24h after the i.a. injection, mice were euthanised and the ipsilateral hippocampi collected at 6 ZTs (every 4h, starting at 8am) for RNAsequencing. Differential expression and rhythmicity analysis were performed using DESeq2 and JTK_CYCLEs tests, respectively. The most significant signalling pathways were assessed by IPA (Ingenuity-Pathway-Analysis) analysis. Results: The number of significantly differentiated genes in epileptogenesis was 4,620 in the light phase (3,549 up- and 1071 down-regulated), while only 3,127 genes (2,786 up- and 341 down-regulated) were differently expressed in the dark phase. The rhythmicity analysis revealed that 1468 genes lost their rhythmicity, while 140 genes acquired new rhythms and only 21 genes kept cycling in both groups. IPA analysis revealed that microglia-mediated neuroinflammation is a key regulator of epileptogenesis, where Toll-like receptors, MAPK and CX3CL1/CX3CR1 pathways were hyperactive in all ZTs. The activation of these pathways triggers the secretion of brain proinflammatory cytokines, apoptosis and microglial activation, respectively. Conclusion: This pioneering study shows that epileptogenesis remaps the hippocampal molecular rhythmicity in mice while exploring key signalling pathways involved in epileptogenesis.