Objective To investigate the serum leptin, leptin receptor of tissue in rats with insulin resistance (IR), and the effect of exercise on them. Methods 9 male Sprague-Dawley rats were fed with normal diet as control group. 34 rats were randomly assigned into 4 groups: model group (n=9), fed with high-fat/high-sucrose diet without any other intervention; metformin group (n=8), fed with high-fat/high-sucrose diet and metformin 300 mg/kg·d; exercise group (n=9), fed with high-fat/high-sucrose diet and trained with swimming; integrated group (n=8), fed with high-fat/high-sucrose diet and metformin 300 mg/kg·d, and trained with swimming. After 6 weeks of intervention,the serum leptin was measured with the enzyme-linked immunoabsorbent assay; the expression of leptin receptor protein in liver, skeletal muscle and adipose were measured with immunohistochemistry, and the expression of leptin receptor mRNA in the same tissues was measured with reverse transcriptase-polymerase chain reaction. Results Compared with the model group, the levels of fasting blood glucose and fasting insulin decreased in the exercise, metformin and integrated group (P<0.05), while the IR index increased (P<0.05). Compared with the control group, the serum leptin increased in the model group (P<0.01), while the expression of leptin receptor protein and mRNA in liver, skeletal muscle and adipose decreased (P<0.01). Compared with the model group, the serum leptin decreased in the exercise, metformin and integrated groups (P<0.05), while the expression of leptin receptor protein and mRNA increased (P<0.05). Compared with the metformin group, the expression of leptin receptor protein and mRNA increased in the exercise and integrated groups (P<0.05). Conclusion High level of serum leptin and low expression of leptin receptor can be found in rats with insulin resistance. Exercise can improve the insulin resistance, which may associate with the decrease of the serum leptin and increases of the leptin receptor.