Social isolation by individual housing the mice eliminates social interaction and induces pathophysiological changes including decreased learning capabilities. Acupuncture with the manipulation of the needles according to traditional Chinese medicine or with the electrical stimulation applied on needles inserted into the acupoints (referred as electro-acupuncture, EA) may modulate stress response, mood, learning and memory process. We investigated whether or not EA could reverse memory impairments induced in the male mouse by social isolation. We also studied any changes due to EA or social isolation in neurotrophic factors as nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) known to have a role in regulating memory and learning processes. We found that 30 min daily session of EA for a period of 4 days at the acupoint Zusanli (low burst frequency of 2 Hz, each pulse was a square electric wave and had a duration of 180, length of 0.1, and internal burst frequency of 80 Hz; intensity 1.0-1.5 mA) reverses the changes in the passive avoidance responses of isolated mice. These findings were associated with decreased NGF and BDNF in the hippocampus and decreased NGF in the striatum of isolated mice exposed to EA. In conclusion the present data in the mouse show that EA may modulate cognition in mice subjected to social isolation.