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Lactic acid bacteria (LAB) are an important group of microorganisms in the food industry. LAB with health benefits are considered natural elements promoting consumer health. The study investigated the anti‐obesity effects of Lactobacillus plantarum CQPC01 (LP‐CQPC01) on high‐fat diet‐induced mice. Liver morphology, liver function indexes, lipid indexes, and inflammatory factors in the serum and liver were determined. Expressions of lipid metabolism‐related gene were also detected by qPCR. LP‐CQPC01 slowed the HFD‐induced increase in body weight, decreased the organ indexes, alleviated hepatic lipid accumulation, and inhibited the increased adipose cell volume. LP‐CQPC01 decreased lipid levels of serum and liver, and the contents of pro‐inflammatory factors, and increased the IL‐4 and IL‐10 contents. LP‐CQPC01 downregulated the expressions of the C/EBP‐α and PPARγ mRNA and upregulated CYP7A1, CPT1, LPL, CAT, SOD1, and SOD2 mRNA. Our results indicated that LP‐CQPC01 is a potential probiotic for preventing or alleviating high‐energy intake‐related lipid conditions. Practical applications: Obesity is a factor of a variety of cardiovascular diseases. Therefore, it is necessary to suppress the occurrence of fat accumulation in time. This study investigated the effect of LP‐CQPC01 on lipid regulation in mice fed a high‐fat diet (HFD) and clarified the mechanism of strain to alleviate obesity by enhancing the decomposition of cholesterol and detoxification of fat. LP‐CQPC01 reduced fat accumulation without oxidative damage, and was confirmed by the attenuated pathological changes of liver. This research can serve as a significant reference for future research, prevention, and treatment of high‐energy intake‐related lipid conditions, and the development of functional foods with anti‐obesity activity. [ABSTRACT FROM AUTHOR]