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Changes in nuclear factor κB (NF-κB) activation induced in peripheral blood mononuclear cells (PBMC) by acute eccentric exercise and by submaximal eccentric training were investigated.Eleven subjects carried out two bouts of eccentric exercise separated by 6 wk of training.Soreness, vertical jump height, and plasma creatine kinase were significantly modified after the first bout. NF-κB activation, p50 and p65, phospho-IκBα and phospho-IKK protein level, and Mn-SOD expression increased in PBMC, whereas IκBα protein level was significantly reduced. Changes were significantly attenuated after the second exercise bout. An additional group of nine subjects carried out the two bouts of exercise without training. Effects on NF-κB activation were similar after the second bout compared with the first, despite a reduction in markers of muscle injury (repeated bout effect).Training significantly attenuates the NF-κB-dependent pathway changes induced in PBMC by eccentric exercise, with no contribution from the repeated bout effect.