Electroacupuncture was performed at the Wangu (GB 12) acupoint, whose position is similar to the cerebellar fastigial nucleus in rats with post-stroke depression. Results showed that the expression of nuclear factor-κB and the levels of tumor necrosis factor-α and interleukin-1β decreased. Simultaneously, the extent of edema in the hippocampus and frontal lobe decreased, and the morphology of the nerve cells recovered to near normal. In addition, fluoxetine treatment displayed a similar effect on post-stroke depression as electroacupuncture at GB 12 acupoint. The results indicate that electroacupuncture at GB 12 acupoint can reduce the levels of cytokines in the hippocampus and frontal lobe of rats with post-stroke depression, and thus provide a neuroprotective effect on post-stroke depression.