Abstract: Objective To investigate the effect of Shenxiong Huayu capsule on the expression of hippocampal CA1 recombinant protein A (small GTP binding protein A, RHOA) and ROCK-2 (RHO associated protein kinase-2, ROCK-Ⅱ). Methods Clean SD male rats (n=96), divided into three groups with 32 rats for each group, gavage was applied 7 days before modeling until the morning of the day to put to death. The groups included the normal control group (normal saline), global cerebral ischemia model group (normal saline) and Shenxiong Huayu capsule+global cerebral ischemia group (Shenxiong Huayu capsule 0.048 g/kg, was dissolved in 0.5 mL double distilled water, once a day, orally 0.3 mL/100 g). Modified Pulsinelli four-vessel occlusion model was constructed in global cerebral ischemia model and Shenxiong Huayu treatment groups and at 1, 3, 7, 14 d after successful modeling, water maze learning test was applied to evaluate the memory abilities of different groups, histopathological changes in HE staining, expression and protein content of RHOA and ROCK-Ⅱ in immunohistochemical staining and Western blot was observed. Results At each time point, escape latency in model group was prolonged (P <0.05) when compared with that in normal control group, and that in Shenxiong Huayu was shorter (P <0.05) than that of model group, but still longer (P <0.05) than that of normal control group. staining showed that, compared with the normal group, model hippocampal CA1 reduced gradually from 1 d to 14 d; an increased survival neurons (P <0.05) in Shenxiong Huayu treatment group at each time points was observed, but still less than that in normal group (P <0.05); immunohistochemistry and Western blot analysis demonstrated that the expression of RHOA and ROCK-Ⅱ in normal control group was not obvious, in model group was decreased after an initial increasing, and that in Shenxiong Huayu treatment group was lower than that of model group (P <0.05), but still higher than that in normal group (P <0.05). Conclusion Shenxiong Huayu capsule improve neuronal damage induced by global ischemia, decreased the expression of hippocampal CA1 region of RHOA and ROCK-Ⅱ.