Progesterone imbalance modulates lipids and fats metabolism leading to obesity. Polyherbal formulation, Fattolin is currently being used in the treatment of obesity but not reported scientifically. Thus the present study investigates the anti-obesity effect of Fattolin in progesterone induced obesity model. Female Swiss albino mice were divided in four groups (n=6) and treated for 28 days, Group I received 2% gum acacia (10 ml/kg); Group II, III and IV received progesterone (10 mg/kg) subcutaneously and Group III and IV further received Fattolin orally at dose of 200 mg/kg and 400 mg/kg respectively. Increased food intake, body weight, liver weight, relative liver weight and, altered exploratory behaviour and biochemical estimations as well as histopathological changeswereobserved in non-treated progesterone control mice. Fattolin treatment (200 and 400 mg/kg) significantly decreased food intake, body weight and liver weight. A significant increase in number of ambulation and rearing and decrease in grooming was also observed. Moreover it significantlydecreased levels of blood glucose, triglycerides, total cholesterol, LDL, VLDL and liver enzymes; however more significant difference was observed with Fattolin 400 mg/kg treatment. Structural abnormality of hepatocytes like mild congestion and focal necrosis induced by progesterone administration was markedly improved with Fattolin treatment at both doses. Thus it can be concluded that, a polyherbal formulation, Fattolin possesses an anti-obesity activity.