Objective At present, there is no special treatment for cirrhotic ascites in modern medicine. Qi Sui Zhu Shui plaster (QSZSP) has been used in ascites. The purpose of this study was to investigate the mechanism of action of QSZSP in the treatment of cirrhotic ascites and its relationship with aquaporin 1 (AQP1). Methods Twenty-four rats were divided into four groups, six rats in each group. Carbon tetrachloride-olive oil is injected into modeling. The control and model groups are treated with blank gel plaster (2 cm × 2 cm), QSZSP low-dose group is treated with Qi Sui Zhu Shui plaster (1 cm × 1 cm), and QSZSP high-dose group is treated with Qi Sui Zhu Shui plaster (2 cm × 2 cm). The changes in body weight and abdominal circumference were measured, the histopathological changes in liver, kidney, and peritoneum were observed in HE staining, the biochemical indexes related to liver function were detected, and the changes in AQP1 expression and the activation of MAPK pathway in the liver, kidney, and peritoneal tissues were evaluated in IHC staining and Western blot. Results After one week of injection of carbon tetrachloride-olive oil, the rats in the model group increased their body weight slowly, the abdominal circumference of the model rats continued to increase with time. After 16 weeks of construction of the cirrhotic ascites model, the liver, kidney, and peritoneum were significantly damaged, and the serum levels of TBiL, AST, ALT, Cr, BUN, K, Na, and Ca in the rats were significantly higher (P < 0.001) and ALB levels were significantly lower (P < 0.001) than those in the control group. After 4 weeks of treatment, the liver, kidney, and peritoneal injury were improved. TBiL, AST, ALT, Cr, BUN, K, Na, and Ca levels were significantly lower (P < 0.001) and ALB levels were significantly higher (P < 0.001) than those in the model group. The protein expression of AQP1, p-ERK, p-JNK, and p-p38 was found to be inhibited in the liver, kidney, and peritoneum. Conclusion QSZSP inhibits the protein expression of AQP1 and MAPK signaling pathway in the liver, peritoneum, and kidney to alleviate liver, kidney, and peritoneal injury caused by cirrhotic ascites, thus reducing the abnormal growth of abdominal circumference.