Curcumin (Cur) has multiple pharmacological effects including antitumor, anti-inflammatory, antioxidant and cardiovascular protective effects. This research aims to further explore whether the cardiovascular protective effects of Cur are mediated by the miR-590-3p/CD40 pathway. Endothelial cells (ECs) were cultivated with 10-7 mol/L angiotensin II (Ang II) to establish a damage model. Real-time PCR was used to determine the expression of CD40 and eNOS mRNA on ECs. The protein expressions of CD40 and eNOS were detected by Western blot analysis. The intracellular activities of SOD, CAT and MDA level were determined by corresponding detection kits, and the level of reactive oxygen species (ROS) in ECs was measured by ROS assay kit. Ang II increased both the mRNA and protein level of CD40, while it down-regulated the expression of eNOS at mRNA and protein level. These observations were accompanied by decreased activities of SOD and CAT with increased levels of intracellular MDA and ROS. Cur and miR-590-3p mimics inhibited the expressions of CD40 mRNA and protein induced by Ang II and alleviated the intracellular oxidative stress seen with increased levels of eNOS. However, these beneficial effects caused by Cur were partially reversed in the presence of miR-590-3p inhibitors. Our results indicate miR-590-3p is involved in the anti-inflammatory effects of Cur in ECs damaged by Ang II.