Sublethal stress stimuli such as systemic endotoxin treatment can induce tolerance of the brain to subsequent ischemic stress, which results in a decreased infarct size. Based on this evidence, we hypothesized that lipopolysaccharide (LPS)-induced preconditioning could protect hippocampal neurons in epileptic rats. To test this hypothesis, the anticonvulsant effect of a low dose of LPS against seizures elicited by pilocarpine hydrochloride was measured. Using the pilocarpine model of temporal lobe epilepsy and LPS-preconditioning, we also investigated hippocampal pathology in the rat brain. Based on the behavioural observations conducted, it can be assumed that the preconditioning procedure used may decrease seizure excitability in epileptic rats. However, determination of the seizure excitability threshold needs to be elaborated. Qualitative and quantitative analyses of histological brain sections in the LPS-preconditioned rats showed markedly decreased intensity of neurodegenerative changes in the CA1, CA3 and DG hippocampal fields. The tendency was observed in all the periods of the pilocarpine model of epilepsy. We suggest that preconditioning with LPS may have neuroprotective effects in the CA1, CA3 and DG hippocampal sectors; however, it has no influence on the course of the seizures in rats in the pilocarpine model of epilepsy.