Objective To investigate the effects of artemisinin (ART) on vascular endothelial cell injury induced by oxidized low density lipoprotein (ox-LDL), and explore its potential molecule mechanism. Methods The human umbilical vein endothelial cells EA.hy926 in logarithmic phase were treated respectively with 0, 50, 100, 150 and 200 mg/ml of ox-LDL and 0, 1,5, 10 and 20 mmol/L of ART. The cell viability were detected by MTT assay. To detected the effect of ART on cells, the EA.hy926 cells were divided into control group (without any treatment), ox-LDL group (treated with 100 mg/ml ox-LDL), ox-LDL+ART group (treated with 100 mg/ml ox-LDL and 10 mmol/L ART) and ox-LDL+ART+3-methyladenine (3-MA) group (treated with 100 mg/ml ox-LDL, 10 mmol/L ART and 5 mmol/L 3-MA). To detected the effect of transient receptor potential channel vanillic acid receptor subtype Ⅳ (TRPV4) on the cells, the EA.hy926 cells were divided into control group, ox-LDL group, ox-LDL+ART group and ox-LDL+ART+ruthenium red (RR) group (treated with 100 mg/ml ox-LDL, 10 mmol/L ART and 10 mmol/L RR). The cell viability were detected by MTT assay. The expressions of TRPV4, autophagy associated proteins (LC3-Ⅱ/LC3-Ⅰ and p62)and apoptosis associated protein (Bcl-2, Bax) were detected by Western blotting. Cell apoptosis were detected by flow cytometry. Results The cell viability of EA.hy926 decreased with the increase of ox-LDL concentration. The viability of ox-LDL induced cells was significantly upregulated by ART (P<0.05). Compared with the control group, the viability of cells, and the expression levels of p62, Bcl-2 and TRPV4 decreased significantly in the ox-LDL group (P<0.05), but the LC3-Ⅱ/LC3-Ⅰ ratio, cell apoptosis rate and expression level of Bax was significantly up-regulated in ox-LDL group (P<0.05). Compared with the ox-LDL group, the cell viability, LC3-Ⅱ/LC3-Ⅰ ratio, the protein expression levels of Bcl-2 and TRPV4 increased significantly, but the cell apoptosis rate, protein expression levels of p62 and Bax decreased significantly in ox-LDL+ART group (P<0.05). Compared with the ox-LDL+ART group, the cell viability, LC3-Ⅱ/LC3-Ⅰ ratio, and protein expression level of Bcl-2 decreased significantly (P<0.05), but the cell apoptosis rate, protein expression levels of p62 and Bax were up-regulated significantly in ox-LDL+ART+3-MA group and ox-LDL+ART+RR group (P<0.05). Conclusion ART can promote autophagy by activating TRPV4 to reduce ox-LDL induced vascular endothelial cell injury.