Aim To study the expression of miR-142-5p in atherosclerosis tissues and its effect on human macrophage apoptosis. Methods Rat atherosclerosis model was constructed, qRT-PCR was used to detect the expression of miR-142-5p in atherosclerotic tissues. 50 μg/L ox-LDL stimulated human macrophage, vascular smooth muscle cell, endothelial cell for 24 h, qRT-PCR was used to detect the expression of miR-142-5p in the cells. Target gene prediction software was used to predict the target gene of miR-142-5p, dual luciferase reporter gene was used to identify the target gene. Cells were transfected with miR-142-5p mimic, mimic control, miR-142-5p inhibitor, inhibitor control into macrophage, Western blot and qRT-PCR were used to to detect the expression of miR-142-5p on target gene, the effect of miR-142-5p and target gene on the apoptosis of macrophages was detected by flow cytometry. Results MiR-142-5p expression was up-regulated in atherosclerotic tissues compared with normal tissue, and the difference was significant (P＜0.01).After stimulation with ox-LDL, the levels of miR-142-5p in vascular smooth muscle cells and endothelial cells did not change significantly compared with before stimulation, but the level of miR-142-5p in the macrophages was significantly higher than that before stimulation (P＜0.01). Predicting the target gene of miR-142-5p was transforming growth factor-β2 (TGF-β2). The luciferase activity was the lowest after transfection with miR-142-5p mimic and TGF-β2. The expression of TGF-β2 protein and mRNA in miR-142-5p mimic group was significantly decreased compared with mimic control group (P＜0.01), the expression of TGF-β2 protein and mRNA in miR-142-5p inhibitor group was significantly higher than that in inhibitor control group (P＜0.01), the apoptosis rate of miR-142-5p mimic group was significantly higher than that of mimic control group (P＜0.01), the apoptosis rate of TGF-β2 siRNA group was significantly higher than that of siRNA control group (P＜0.01). Conclusion MiR-142-5p was over expressed in atherosclerosis tissues, and miR-142-5p could promote the apoptosis of human macrophages by regulating the target gene TGF-β2.