ABSTRACT Intermittent fasting (IF) has an increasingly role of lose weight in overweight and normal weight individuals. The present study was investigated that the effects of intermittent fasting with high fat/low carb diet on obese rats. Forty-two adult male albino rats weighting (185± 10 g) were randomly divided into 6 equal groups (n=7). Group 1 was fed on basal diet (as negative control group). Group 2 was fed on basal diet and fasted (as positive control group). Groups of rats (3:6) were fasted 24 hours for 3 nonconsecutive day/week. Group 3 was fed on 20%, 20%, and 60% of energy from fat, protein, and carbohydrate, respectively. Group 4 was fed on 30%, 20%, 50% of energy from fat, protein, and carbohydrate, respectively, group 5 was fed on 40%, 20%, 40% of energy from fat, protein, and carbohydrate, respectively, group 6 was fed on 50%, 20%, 30% of energy from fat, protein, and carbohydrate, respectively. Rats weighed twice a week and weight gain was calculated. At the last week of the feeding trial, 3 rats from each group were injected using 0.1 ml formalin (4%) to induce inflammation. At the end of experimental period (8 weeks) the rats were euthanized and blood samples were withdrawn for separating the serum were collected for biochemical analysis. Peritoneal fat pad was dissected and weighed. Blood glucose level, insulin concentration, leptin concentration, lipid profile (TC, TG, HDL-c, LDL-c and VLDL-c), liver functions (AST and ALT) and kidney functions (creatinine and uric acid) were determined. The results showed that fasting (24 h of fasting nonconsecutive day/week) combination with basal diet caused a significant decrease (P<0.05) in weight gain, feed intake, peritoneal fat pad, serum (glucose, insulin, leptin, ALT, AST, uric acid, creatinine, TC, TG, LDL-c, VLDL-c) and significant increase (P<0.05) in HDL-c level compared to the control group (–ve). Group of rats were fed 50%fat, 20%protein, 30% carbohydrates had best result in weight loss compared other tested groups. In conclusion, IF has beneficial effects even with the continuity of the obesogenic diet and proinflammatory diet in obese rats. IF combination with diet administration of high fat/low carb could be beneficial method for weight loss but has many side effect on health status.