coronary heart disease (cHd) is the leading cause of human morbidity and mortality worldwide. Microrna (mirna) profiling is an innovative method of identifying biomarkers for many diseases and may be a powerful tool in the diagnosis and treatment of cHd. The present study aimed to analyze the effects of miRNA (miR)-381 on the inflammatory damage of endothelial cells during cHd. a total of 21 patients with cHd and 21 healthy control patients were enrolled in this study. reverse transcription-quantitative PCR, western blotting and immunofluorescence assays were conducted to examine the expression levels of mir-381, c-X-c chemokine receptor type 4 (cXcr4), Bcl-2, Bax, cleaved-caspases-3 and-9, p38, erK1/2 and JnK. cell Counting Kit-8, EdU and flow cytometry experiments were performed to evaluate cell proliferation and apoptosis. an ELISA was adopted to determine the expressions of inflammatory factors (interleukins-8,-6 and-1β, and tumor necrosis factor-α). in addition, a dual-luciferase reporter assay was used to determine the relationship between mir-381 and cXcr4. decreased mir-381 expression and increased cXcr4 expression in the plasma were observed in the cHd group compared with the normal group, which indicated a negative relationship between mir-381 and cXcr4. overexpression of mir-381 significantly promoted the proliferation and inhibited the apoptosis of oxidized low-density lipoprotein (oX-ldl)-induced human umbilical vein endothelial cells (HuVecs) through mitogen-activated protein kinase pathway by targeting and inhibiting cXcr4. Furthermore, overexpression of miR-381 reduced the release of inflammatory factors in oX-ldl-induced HuVecs. By contrast, reduced expression of mir-381 exerted the opposite effects, which were subsequently reversed by silencing cXcr4 expression. results from the present study indicated that mir-381 was a cHd-related factor that may serve as a potential molecular target for cHd treatment.