Objective To observe the changes of non-alcoholic fatty liver related indices in diet-induced obesity-resistant rats and diet-induced obesity rats. Methods A total of 140 male Sprague Dawley(SD) rats were randomly divided into normal control group (n=20, normal diet for 8 weeks) and model group (n=120, high fat diet for 8 weeks). The rats of model group were further divided into 2 groups: O-N (obesity with non-alcoholic fatty liver) and OR-N (obesity-resistance with non-alcoholic fatty liver) groups. The rats with body mass higher than mean +1.96 folds standard deviation were included in O-N group and those with body mass lower than mean +1.0 fold standard deviation were included in OR-N group. The animals with the top 20 weight gains in the O-N group and those with the least 20 weight gains in OR-N group were used in the present study. The general conditions and weight changes of rats were dynamically observed for 8 weeks. Eight rats were sacrificed in each group at the end of the 8th week and the following indices were compared among the three groups,including serum levels of alanine aminotransferase (ALT), total cholesterol(TC), triglyceride(TG), high-density lipoprotein (HDL), insulin sensitivity index(ISI), leptin, energy utilization and body fat ratio. The pathological changes of liver tissues were observed by H-E staining. Results The weight difference of rats in the O-N group and the OR-N group gradually increased; at the end of the 8th week, the weight of rats in O-N group was significantly higher than those in the OR-N group and the normal control group(P<0.01). The serum levels of ALT, TG, and leptin were significantly increased in both O-N and OR-N groups (P<0.05,P<0.01). The TC, TG, leptin levels and energy utilization in O-N group were significantly higher than those in OR-N group (P<0.05, P<0.01). The HDL and ISI levels in the O-N group were significantly lower than those in the OR-N and normal control groups (P<0.01, P<0.05). Light microscopy showed a great number of fat vacuoles in the liver cells of O-N and OR-N groups. Conclusion High fat diets can induce SD rat to develop non-alcoholic fatty liver with obesity and obesity-resistance.Increase in serum leptin and ISI may play a role in resisting diet-induced obesity and non-alcoholic fatty liver of rats.