OBJECTIVE To assess the effect of restricting calories with or without daidzein on weight, serum levels of glucose, and inflammatory markers in obese rats. METHODS This experimental study was carried out in Jundishapur University, Ahvaz, Iran, from September 2010 to January 2011. Obesity was induced in 30 male Wistar rats (140-160, 6-8 weeks age) after 6 weeks by feeding them a high-fat diet. Then, the rats were divided into 3 groups: obese rats treated with low-calorie diet containing 50 mg/kg daidzein (n=10); obese rats treated with low-calorie diet containing dimethyl sulfoxide (n=10); and obese rats that were given ad libitum access to food as the control group (n=10). After 4 weeks, blood samples were collected in order to analyze the levels of glucose, resistin, and high sensitive C-reactive protein (CRP). RESULTS Restriction of calories resulted in decreased blood glucose (p=0.002), and decreased levels of high sensitive CRP (p=0.000), but had no significant effect on resistin level. Daidzein administration had no significant effect on body weight, serum glucose, levels of resistin, and high sensitive CRP. CONCLUSIONS Calorie restriction significantly affected body weight, serum glucose, low-grade inflammation biomarkers, and masked the effect of daidzein.