Aim To investigate the effect and mechanism of Erchen decoction and Taohong Siwu decoction containing serum on oxidized low density lipoprotein (ox-LDL) induced endothelial cell damage. Methods EA.hy926 cells were cultured in vitro, then randomly divided into control group, ox-LDL group, intervention group, inhibitor group.Cell apoptosis was detected by flow cytometry, malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) activity were detected by colorimetry, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in cell supernatant were detected by ELISA, and phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT (p-AKT) and endothelial nitric oxide synthase (eNOS) protein expressions were detected by Western blot. Results Compared with control group, the level of TNF-α and IL-6 increased significantly (P＜0.01), MDA content in cells increased significantly (P＜0.01), SOD activity decreased (P＜0.05), NO level in supernatant decreased significantly (P＜0.01), content of reactive oxygen species (ROS) and apoptosis rate increased significantly, the protein expression level of PI3K, eNOS and the protein phosphorylation of AKT were significantly decreased (P＜0.01) in ox-LDL group. Compared with ox-LDL group, the level of TNF-α and IL-6 in cell supernatant decreased significantly (P＜0.01), MDA content in cells decreased significantly (P＜0.01), SOD activity increased significantly (P＜0.05), NO level in the supernatant increased significantly (P＜0.01), ROS content and apoptosis rate decreased significantly, the protein expression level of PI3K, eNOS and the protein phosphorylation of AKT were significantly increased (P＜0.01) in intervention group. Compared with intervention group, the level of TNF-α and IL-6 increased significantly (P＜0.01), MDA content in cells increased significantly (P＜0.01), SOD activity decreased (P＜0.05), NO level in supernatant decreased significantly (P＜0.05), content of ROS and apoptosis rate increased significantly, the protein expression level of PI3K, eNOS and the protein phosphorylation of AKT were significantly decreased (P＜0.01) in inhibitor group. Conclusion The serum containing of Erchen decoction and Taohong Siwu decoction can effectively protect ox-LDL induced endothelial cell injury, which may be related to activation of PI3K/AKT/eNOS signaling pathway.