Many studies indicate that intravenous immunoglobulin (IgG) therapy may decrease symptoms of epilepsy. In this study, we assessed the effects of intravenous IgG in an experimental rat kindling model and attempted to elucidate the underlying mechanism of the IgG effect. For induction of kindling, Wistar rats received repeated intraperitoneal injections of picrotoxin. The serum level of neuron-specific enolase (NSE) was measured to determine seizure severity. Interferon (IFN)-gamma and interleukin (IL)-6 levels were measured in rat hippocampus homogenates. The serum NSE level and hippocampal IFN-gamma level were significantly higher in fully kindled, untreated rats compared to unkindled control rats, whereas IL-6 levels were similar in all groups. Intravenous IgG-treated kindled rats showed NSE and IFN-gamma levels similar to those of control rats, along with lower seizure severity and longer seizure latent period than fully kindled, untreated rats. These results indicate that intravenous immunoglobulin exerts a protective effect on the neurons of kindled rats, potentially by downregulating cytokines in the brain. These results shed light on the mechanism by which intravenous immunoglobulin decreases the severity of epileptic seizures.