Objective To explore the effect of evening primrose oil (EPO) on aortic endothelial damage in rats with polycystic ovary syndrome (PCOS), using network pharmacology and in vivo experiments. Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling (RAS) pathway were verified by experiments. Fifty-eight female SD rats were divided randomly into a blank group (n= 10) and a modeling group (n = 48). Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks. The PCOS model was prepared at week 6 by administration of letrozole (1 mg / (kg·d)) for 21 days. Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels. The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks. Blood, blood vessels, and ovaries were then collected. Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone (LH), testosterone (T), follicle-stimulating hormone (FSH), endothelin (ET-1), and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay ( ELISA). Serum levels of nitric oxide ( NO) were determined by spectrophotometry. Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry. Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis. Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways, including RAS. Serum levels of ET-1, FSH, LH,and T measured by ELISA were significantly decreased after EPO treatment, compared with the model group (P<0. 01). EPO significantly decreased the expression levels of AngⅠ, VEGF-B, AT₂R, ET-1, and TNF-α proteins in the aorta (P<0. 01) and significantly increased expression levels of Ang Ⅱ, CD31, and endothelial NO synthase proteins ( P<0. 01). Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/ Ang Ⅱ/ AT1 axis.