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Probiotics are regard as safety approaches for preventing and treating some chronic diseases. This study investigated the regulating effect of Lactobacillus plantarum CQPC03 (LP‐CQPC03) on lipid metabolism in high‐fat diet (HFD)‐induced obesity in mice. The results showed that administration of LP‐CQPC03 at a concentration of 1.0 × 109 CFU/kg body weight inhibits HFD‐induced obesity and improves lipid metabolism in the liver and serum. LP‐CQPC03 intervention attenuated obesity‐induced hepatic tissue damage, led decreases in hepatic triglyceride (42.02 mmol/gprot), total cholesterol (3.85 mmol/gprot), and LDL‐C (1.03 mmol/gprot), and an increase in HDL‐C (1.07 mmol/gprot). The same tendencies were observed in serum of HFD‐fed mice. LP‐CQPC03 intervention led a decrease in serum levels of aspartic transaminase, alanine transaminase, and alkaline phosphatase. LP‐CQPC03 alleviated inflammation by increasing the level of interleukin (IL)‐4 and IL‐10, and decreasing the levels of pro‐inflammatory factors, including IL‐6, IL‐1β, tumor necrosis factor‐α, and interferon‐γ. LP‐CQPC03 also increased activities of SOD and GSH‐Px in liver significantly and dropped the hepatic malondialdehyde (MDA) level from 3.39 nmol/gprot to 1.90 nmol/gprot. RT‐qPCR results showed that the lipid metabolism‐improving effect of LP‐CQPC03 was performed by upregulating the expression of carnitine palmitoyltransferase 1, lipoprotein lipase, catalase, and superoxide dismutase 1. This study indicates that L. plantarum CQPC03 might be a potential probiotic that can help mitigate the adverse effects of excessive lipids on the liver, and prevent or alleviate high‐energy intake‐related obesity. Practical applications: Intaking high‐energy foods is a potential risk of lipid metabolic disorder. Therefore, it is necessary to seek an effective and safe approach for preventing the obesity‐related disease. This study found that LP‐CQPC03 limited the rate of increase in body weight of mice fed on HFD, maintained normal hepatic tissue morphology, and exhibited a strong regulating effect on lipid metabolism. And the threshold concentration of LP‐CQPC03 for the lipid‐lowering effect was 1.0 × 109 CFU/kg body weight. Therefore, LP‐CQPC03 is a potential probiotic for preventing or alleviating high‐energy intake‐related obesity. [ABSTRACT FROM AUTHOR]