Atherosclerosis is a chronic inflammatory disease, which is due to abnormal lipid metabolism in the body that causes excessive cholesterol-rich lipoproteins to accumulate in the arterial wall, resulting in thickening and hardening of arterial wall, decreasing its elasticity and lumen stenosis. Low-dose laser therapy (LDLT) has been reported to possess cardioprotective effects whereas there is no consensus on the underlying mechanisms. This study aimed to explore whether LDLT could ameliorate atherosclerosis and explore the potential molecular mechanisms. ApoE–/– mice were fed with a high-fat diet (HFD) for 18 weeks to develop atherosclerotic lesions, and were treated with LDLT daily in the last 10 weeks. After the treatment, the aorta, heart, liver and other tissues of the mice were taken for histological staining and polymerase chain reaction (PCR) to determine the development of atherosclerosis in the mice. The experimental results showed that the LDLT-treated mice had a smaller aortic plaque area and less lipid deposits in liver than the control mice did. In addition, the results of real time quantitative PCR (RT-qPCR) showed that LDLT treatment significantly downregulated the expression of sterol regulatory element-binding protein 2 (Srebp2) and 3-hydroxy-3-methylglutaryl CoA reductase (Hmgcr), which were involved in liver cholesterol synthesis. These results indicated that LDLT could improve the body’s lipid metabolism and has a protective effect on cardiovascular diseases.