Abstract：Objective：To study the effect of puerarin injection on cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/aquaporin 4(AQP4) pathway and brain edema in model rats with subarachnoid hemorrhage(SAH). Methods：A total of 78 male SD rats were divided into the sham operation group，the model group，the puerarin injection groups of low-dose，medium-dose and high-dose respectively(the low-dose，medium-dose and high-dose groups) and the positive medicine group. Except for the sham operation group， the other groups were given injections of femoral arterial blood into cisterna magna for deposition twice. After building the SAH model of rats，the sham operation group and the model group were given intraperitoneal injection of 2 mL saline； the low- dose， medium- dose and high- dose groups were respectively given puerarin injection according to the dose of 50，100，200 mg/(kg·d)；the positive medicine group was given dexamethasone sodium phosphate injection according to the dose of 0.5 mg/(kg·d). The nerve function was scored；the brain water content was measured；the levels of cAMP and PKA in cerebrospinal fluid were detected by Elisa；the levels of mRNA and protein in PKA and AQP4 in brain tissue were detected by RT- PCR and Western blot. Results： Compared with those in the sham operation group，the score of nerve function，the brain water content，the contents of cAMP and PKA in cerebrospinal fluid and the levels of mRNA and protein in PKA and AQP4 in brain tissue in the model group were significantly increased(P＜0.05).Compared with those in the model group，the scores of nerve function，the brain water content，the contents of cAMP and PKA in cerebrospinal fluid and the levels of mRNA and protein in PKA and AQP4 in brain tissue in the positive medicine group，the medium-dose group and high-dose group，as well as the brain water content and the levels of mRNA and protein in PKA and AQP4 in brain tissue in the low-dose group were significantly decreased(P＜0.05). Compared with those in the positive medicine group，the scores of nerve function，the contents of cAMP and PKA in cerebrospinal fluid and the levels of mRNA and protein in AQP4 in brain tissue in the medium-dose and high-dose groups，as well as the brain water content and the levels of mRNA and protein in PKA in brain tissue in the low-dose group were significantly increased(P＜0.05). Compared with those in the low-dose group，the scores of nerve function in the medium-dose and high-dose groups，as well as the brain water content，PKA content in cerebrospinal fluid，the levels of mRNA and protein in PKA and AQP4 in brain tissue in the high-dose group were significantly decreased(P＜0.05). Compared with those in the medium-dose group，the score of nerve function and the level of protein in AQP4 in brain tissue in the high-dose group were significantly decreased(P ＜ 0.05).Conclusion： By regulating the cAMP/PKA/AQP4 pathway， puerarin can reduce the effect of AQP4 to reduce the subarachnoid hydrops and alleviate SAH.