For ictogenesis, initial step is intrinsic bursts of pacemaker neurons and, through exaggerated circuits or networks, the involved neurons become hyperexcitable state. Hypersynchrony of hyperexcitable neurons can induce paroxysmal depolarization shift for developing seizure. The mechanism underlying the development of post-traumatic epilepsy still remains to be elucidated. By traumatic brain injury, breakdown of blood-brain barrier (BBB) may lead network changes, long-lasting epileptiform activity and eventual neurodegeneration. Recently the concept of inflammation and epileptogenesis is widely accepted. In the surgically resected brain tissue from refractory partial epilepsy patients, there are hallmarks of a chronic inflammatory state and, also, via animal experiments, we can find the role of inflammation in the genesis of seizure and epilepsy. Inflammatory mediators (IL-1b, TGF-β1 and COX-2) are associated with the epileptogenic brain. They can reduce seizure threshold, induce neurodegeneration, neurogenesis, and synaptic plasticity, and also disregulate BBB permeability. The increase in knowledge about a role of inflammation in epileptogenesis may support the use of specific anti-inflammatory drugs for developing disease-modifying treatments that can interfere epileptogenesis.