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Objective Growing evidences suggest that electroacupuncture (EA) can improve traumatic stress-induced immuno-depression, but the mechanism needs further study.In the present study, the contribution of EA on the neuroimmune modulation, as well as the involvement of calreticulin (CRT)-c-Src pathway in the traumatic stress was investigated.Methods Two age groups of rats (3 month and 18 month) were undergone traumatic stress.EA was performed on bilateral acupoints zusanli (ST36) and sanyinjiao (SP6).Immune consequences, cortical CRT and c-Src expression were detected by Western blot, immunofluorescence and CCK8 respectively.A long-term neuron culture was also used herein, time-lapse effect of lipopolysaccharide (LPS) on CRT-c-Src pathway was analyzed.Results (1) Traumatic stress resulted in a suppression in lymphocyte proliferation and NK cell activity with age dependent manner, EA stimulation could significantly improve this immuno-suppression.(2) The age-dependent immuno-suppression was due to different triggering in CRT-c-Src pathway in cortical neuron.(3) Central modulation of CRT inflenced c-Src expression, in the meantime improved traumatic stress induced immuno-suppression.Conclusion EA could age-dependently improved traumatic stress induced immuno-suppression, the effect was proposed to correlated with CRT-c-Src pathway in cortical neuron.