AIM: To investigate the inhibitory effect of As2O3 on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro.METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901.The animals were randomly divided into three groups.As2O3 was injected into the arsenic-treated groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected into the control group. Microvessel density (MVD) and expression of VEGF were detected with immunofluorescence laser confocal technology.Further expression of VEGF protein and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT- PCR in SGC-7901 cells treated with As2O3.RESULTS: In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As2O3 respectively, about 50% and 30%tumor growth inhibition were observed correspondingly (P ＜ 0.05, P ＜ 0.05). Decrease in MVD appeared in As2O3-treated tumors compared with control group (P ＜0.001, P ＜ 0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5 mg/kg group (P ＜ 0.01).The fluorescence intensity levels of VEGF in tumor cells were significantly lowered in the arsenic-treated groups (P ＜ 0.01, P ＜ 0.01). The fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5 mg/kg group (P ＜ 0.01). In vitro, the expression of VEGF protein decreased in dose- and time-dependent manner after the treatment with As2O3, but in VEGF mRNA no significant difference was found between the control group and the treated groups.CONCLUSION: As2O3 can inhibit solid tumor growth by inhibiting the formation of new blood vessels. One of the mechanisms is that As2O3 can inhibit VEGF protein expression.