Regular swimming and phytotherapeutic supplementation are assumed to alleviate the severity of neurodegeneration leading to dementia. The effect of swimming training and that of enriched lab chow containing 1% (w/w) dried nettle (Urtica dioica) leaf on the prevention of severity of brain injury caused by N-methyl-d-aspartate (NMDA) lesion in Wistar rats were investigated. Nettle supplementation and regular swimming exercise seem to improve the adverse effect of brain injury caused by NMDA lesion assessed by passive avoidance test and open-field test. Nettle supplementation decreases the level of reactive oxygen species, measured by electron paramagnetic resonance, and the DNA-binding activity of NF-kappaB. The data reveal that nettle supplementation has an effective antioxidant role, down-regulates the inflammatory transcription factors and could also promote learning performance in the brain. Regular swimming increases the concentration of reactive species in the cerebellum and alters the activity of transcription factors toward inflammation. The additive effect of the two treatments was more profound in the down-regulation of inflammatory transcription processes in NMDA lesion.