BackgroundObesity is a major health problem worldwide and risk factor for various cardiovascular diseases. High-Fat Diet (HFD) induced obesity in rats was an effective model to evaluate anti-obesity activities of drugs. Cromolyn sodium described as a mast cell stabilizer and Chlorpheniramine maleate used as an antihistaminic and prevents allergic inflammation. They also decreased the release of inflammatory mediators from mast cells. Mast cells were found to involve directly in obesity and diabetes. ObjectiveThe aim of this study was to determine the impact of Cromolyn sodium and Chlorpheniramine Maleate alone and the combination therapy of both on HFD induced rats. Experimentthe experiment was designed by supplementing HFD to rats for 49 days to induce obesity. The obese rats were treated with different drugs individually and in combination. Serum lipid parameters and Liver function parameters were observed and found a change in lipoproteins along with increased body weight, the mRNA of leptin, adiponectin and resistin in visceral adipose tissue were determined by quantitative real time-PCR. ConclusionChronic administration of Cromolyn Sodium (50 mg/kg) and its combination with Chlorpheniramine Maleate at a sub maximal dose (5 mg/kg & 25 mg/kg) reversed all the parameters significantly than Chlorpheniramine (10 mg/kg) alone, which was altered due to HFD. The combination showed effects directly on adipokines of visceral tissue and found a suitable candidate in treatment of metabolic syndrome.