Objective To verify the inhibitory effect of Xiaoshui Formula（XSF）on malignant pleural effusion（MPE）in animal level and explore its mechanism. Methods After MPE mice model was established,the volume of MPE,survival time,pleural metastasis,pleural permeability and angiogenesis,vascular endothelial growth factor（VEGF）expression were assessed using bioluminescence imaging,Luminex and immunohistochemistry. Results The MPE volume of mice in XSF group was significantly reduced and the survival time was prolonged. There was no significant difference between the XSF group and the control group in pleural metastases. The Evans’ blue ratio of MPE to peripheral serum,the level of VEGF in MPE,and the expression of CD31 and CD34 in pleural tumors were much lowered in XSF group than that of the control group all with statistically significant difference. Conclusion Xiaoshui Formula can inhibit the production of MPE in mice,and its mechanism may be related to reducing pleural permeability and inhibiting angiogenesis.