It remains unclear whether prolonged febrile seizures (pFS) in childhood facilitate mesial temporal lobe epilepsy (MTLE) in adulthood. Interleukin (IL)-1β is associated with seizures in children and immature animal models. Here, we use a rat model of pFS to study the effects of IL-1β on adult epileptogenesis, hippocampal damage, and cognition. We produced prolonged hyperthermia-induced seizures on postnatal days (P) 10-11 and administered IL-1β or saline intranasally immediately after the seizures. Motor and cognitive functions were assessed at P85 using rotarod and passive avoidance tests. Electroencephalogram recordings were conducted at P90 and P120. Hippocampal CA1 and CA3 neurons and gliosis were quantified at the end of the experiment. Spontaneous seizure incidence was significantly greater in rats that had received IL-1β than in those that had received saline or those without hyperthermia-induced seizures (p < 0.05). Seizure frequency did not differ significantly between the three groups and no motor deficits were observed. Passive avoidance learning was impaired in rats that received IL-1β compared with controls (p < 0.05), but was not different from that in rats that received saline. Hippocampal cell numbers and gliosis did not differ between the three groups. These results indicate that neuronal loss and gliosis are not prerequisites for the epileptogenic process that follows pFS. Our results suggest that infantile pFS combined with IL-1β overproduction can enhance adulthood epileptogenesis, and might contribute to the development of MTLE.