OBJECTIVE To investigate the effects of arsenic pentaoxide (As2O5) on the proliferation and apoptosis of endothelial cells and compare the effect of As2O5 and arsenic trioxide (As2O3) in vitro. METHODS Human umbilical vein endothelial cells (HUVEC) were incubated with or without As2O5 or As2O3 for a certain period. The proliferation profile of HUVEC was determined by methyl thiazolyl tetrazolium (MTT) method. The apoptosis of HUVEC was detected by microscopy and flow cytometry (FCM). RESULTS As shown by MTT assay, the viabilities of HUVEC were (72.5 +/- 13.8)%, (52.9 +/- 6.2)%, (15.0 +/- 12.8)%, and (13.8 +/- 13.2)%, respectively, in 0.5, 1.0, 5.0, and 10.0 mg/L As2O5 groups, of which the viabilities of HUVEC at 1.0, 5.0, and 10.0 mg/L of As2O5 were significantly lower than controls (P = 0.006, 0.007, and 0.008); however, the viability was not significantly different between 5.0 and 10.0 mg/L As2O5 groups (P = 0.119). In 1.0 mg/L As2O5 group, the cell viabilities were (88.4 +/- 6.3)%, (53.1 +/- 8.8)%, (30.7 +/- 7.9)%, and (16.3 +/- 4.6)%, respectively, at 24, 48, 72, and 96 h, of which the cell viabilities at 48, 72, and 96 h were significantly lower than controls (P = 0.042, 0.025, and 0.012). As2O5-induced apoptosis of HUVEC was observed by phase contrast microscope and flow cytometry with Annexin V/PI staining. After 48 hours of incubation, the IC50s of As2O5 and As2O3 were 1.1 and 0.3 mg/L, respectively. CONCLUSIONS As2O5 can inhibit the proliferation of HUVEC and the minimum effective concentration is 1 mg/L. Apoptosis is the main way that As2O5 induces the death of HUVEC. The inhibitory effect of As2O5 on HUVEC is weaker than that of As2O3.