OBJECTIVE To explore the effect of Shenxiong Huayu Capsule (SHC) on the cerebral ischemia-reperfusion (IR) injury and the expression of growth associated protein 43 (GAP43) after total cerebral IR in the hippocampal CA1 region of rats. METHODS Totally 100 male adult SD rats were randomly divided into five groups, i.e., the control group, the model group, the group A (by taking SHC once daily), the group B (by taking SHC twice daily), and the group C (by taking SHC thrice daily), 20 in each group. The total IR model was prepared by improved Pulsinelli's 4-vessel occlusion method. Morphological changes of the hippocampal CA1 region were observed by HE staining at day 1, 3, 7, and 14. The expression of GAP43 in the hippocampal CA1 region was detected using immunohistochemical assay at day 1, 3, 7, and 14. Meanwhile, the behavioral score was determined. The expression of GAP43 in the hippocampal CA1 region was detected using Western blot at day 14. RESULTS Compared with the control group, the expression of GAP43 increased in the model group, the behavioral score was elevated, degenerated neurons increased, and survival neurons decreased in the model group (all P < 0.05). Compared with the model group, the expression of GAP-43 increased (with the most significant difference seen in the group C, P < 0.01), the behavioral score significantly decreased, degenerated neurons decreased, and survival neurons increased in each HSC group (all P < 0.05). Survival neurons obviously increased at day 14, of which, most number of survival neurons and highest contents of GAP43 protein could be seen in the group C, showing statistical difference when compared with those of the group A and the group B (P < 0.01). CONCLUSIONS SHC had protective effect on total cerebral IR in the hippocampal CA1, which might be associated with increased expression of GAP43.