Abstract: Objective To investigate the effect of arsenic trioxide (As₂O₃) on malignant pleural effusion (MPE) in mice model caused by lung cancer. Methods Eighty-four MPE mice models were established firstly. Random allocation was taken to divide them into three groups: experimental group, negative control and positive control. As₂O₃was intraperitoneally injected into mice of experimental group, normal saline and bleomycin were administered to negative control and positive control respectively, with the same dose for a week. After administration, MPE volume was measured, expressions of VEGF and VEGF mRNA in MPE were detected by ELISA and RT-PCR, overall survival of MPE mice was analyzed by Kaplan-Meier. Results After administration of As₂O₃, MPE volume was attenuated significantly in experimental group when compared with negative control (0.43±0.11) ml vs (0.92±0.53) ml, P=0.000, and positive control (0.43±0.11) ml vs (0.63±0.32) ml, P=0.001, and the expression of VEGF in MPE of As₂O₃group was remarkably lower than those of negative control (493.07±35.10)pg/ml vs (2500.30±210.32)pg/ml, P=0.001 and positive control (493.07±35.10) pg/ml vs (671.23±34.21) pg/ml, P=0.003. Compared with negative and positive controls, VEGF mRNA expression level in MPE decreased significantly after intervened with As₂O₃(0.32±0.02) vs (1.02±0.32), P=0.001; (0.32±0.02) vs (0.53±0.04), P=0.004. The survival time of mice in As₂O₃group was (21.20±2.86) d, which was significantly longer than those of negative control (13.05±3.50) d, P=0.031 and positive control (17.60±3.22) d, P=0.013. Conclusion The results suggest that As₂O₃inhibits MPE promotion and lengthen mice' survival time by reducing transcription and expression of VEGF. This study provides basis by animal experiment for MPE treatment.