Abstract:[Objective] As a metabolic syndromes disease, obesity has become an epidemic hazard and a major problem for health care systems worldwide. It is well documented that n-3 polyunsaturated fatty acids (n-3 PUFAs), especially docosahexaenoic acid (DHA), could effectively prevent and treat obesity and related diseases. Aim to study the effect of DHA from Schizochytrium sp. on high-fat-induced obesity in male C57BL/6J mice, including the weight of body and adipose tissue of the mice and the content of blood lipid, pharmacological changes in liver and fat tissue, and the expression level of lipid metabolism related gene. [Methods] Mice were fed with high fat diet for nine weeks, and mice whose weight gain was 15% higher than the control were selected for the follow-up experiment. Mice were divided into five groups: (1) low fat diet as the control; (2) high fat diet as the model control; (3) high fat diet + microalgal oil with 50 mg DHA/kg body weight; (4) high fat diet + microalgal oil with 100 mg DHA/kg body weight; (5) high fat diet + microalgal oil with 200 mg DHA/kg body weight. Mice in groups of (1) and (2) were gavaged with isovolumetric corn oil, and mice in groups of (3), (4) and (5) were gavaged with microalgal oil with different dosage adjusted by corn oil. After nine weeks treatment, the mice were anesthetized, and blood samples were obtained from venosus plexus of fundus oculi. The total triglyceride, total cholesterol and high-density lipoprotein cholesterol in the serum were measured. Body, adipose tissue and liver of the mice were weighted, and the morphological changes of fat and liver were observed and the lipid metabolism related gene was examined. [Results] Microalgal oil DHA from Schizochytrium sp. significantly decreased the abnormal fat accumulation and blood lipid levels of the obesity mice, improved liver and fat tissue morphology, and promoted the expression of hormone sensitive lipase gene in white tissue fat. [Conclusion] Microalgal oil DHA from Schizochytrium sp. might have prospective applications in obesity therapy.