Cerebral ischemia induces rapid neuro-immunological injury as demonstrated by changes in inflammatory factors, cytokines and chemokines in the circulation and peripheral immune system. In addition, elevated acetylcholinesterase (AChE) activity was reported in ischemic brain tissue. Here, we evaluated the time dependent changes in AChE levels and cytokines and NK activity, as well as the relationship of AChE to apoptosis in the brain, spleen and thymus at different time points after focal cerebral ischemia. The data show an elevated level of immunoreactive AChE in the cortex of ischemic brains. This sustained elevated level of AChE in the brain, thymus and spleen activates capase-3 in response to cerebral ischemia. We propose that this pro-apoptotic activity may result in a T helper cell (Th1/Th2) imbalance and impaired immune function in ischemia.