Objective:To study the effects of Penehyclidine Hydrochloride on the expression of nuclear factor-κB in rats after acute global cerebral ischemia/reperfusion injury. Methods:Sprage-Dawley rats were randomly divided into four groups: Group S (sham operation group, n=24), Group IR (ischemia/reperfusion, n=24), Group A (Anisodamine treated group, n=24), Group P (Penehyclidine Hydrochloride treated group, n=24). The model of global ischemia and reperfusion was established in Group IR,Group A and group P by Pulsinelli's method. The activation of nuclear factor-κB in brain tissue after ischemia 10 minutes and reperfusion for 2,6,12,24 hours were examined by immunohistochemical method, and HE staining were also performed to detect the injury of brain tissue. Results:The activation of nuclear factor-κB began to increase at 2 hours after reperfusion, increased to the highest peak at 6 hours, and then gradually decreased. With the reperfusion prolonged, the number of abnormal nurons including degeneration and necrosis significantly increased. Compared with Group IR, the activations of nuclear factor-κB in Group A and Group P decreased at every time point, and at 6 hours and 12hours the activations were belower in Group P than in Group A. Conclusions: Penehyclidine Hydrochloride could protect the brain tissue from acute global ischemia/reperfusion injury, and the mechanism might be related to its decreasing the activation of nuclear factor-κB, and the effects were better than Anisodamine.