Objectives To explore effect of lipitor on apoptosis and phosphatidyl inositol-3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signal pathway in high glucose-induced human umbilical vein endothelial cell (HUVEC). Methods The cases were randomly divided into normal control group, model control group (33.3 mol/L glucose), lipitor low, medium, high-dose group (0.1, 1, 10 μmol/L lipitor).The viability of HUVEC was detected by MTT assay. The morphology of HUVEC was photographed by inverted microscope. The apoptosis of HUVEC was examed by Annexin V-FITC/PI flow dual-staining method. The concertration of NO in HUVEC supernatant was exmaed by Gries method. The activation of PI3K/AKT and expression of eNOS was assayed by western blot. Results HUVEC was shrinkage, rounded and brighten, the viability of HUVEC decreased, early and late apoptosis rate of HUVEC increased significantly, the level of NO, eNOS, PI3K and AKT phosphorylation also reduced in model control group (P < 0.01). 1, 10 μmol/L lipitor improved HUVEC morphology, increased HUVEC' viability and expression of PI3K (P < 0.05). 0.1, 1, 10 μmol/L lipitor suppressed HUVEC' apoptosis, increased the concentration of NO, expression of eNOS and phosphorylation of AKT (P < 0.05). Conclusion These results suggested lipitor exert anti-apoptosis in high glucose -induced HUVEC, which might be related to PI3K/AKT/eNOS signal pathway.