The influence of a palatable, high-energy diet, and exercise training on the levels of serum total cholesterol (CHOL) and CHOL carried by high-density lipoproteins (HDL CHOL) was investigated. Female rats were fed either a laboratory chow or a diet made of palatable food items containing a high level of fat. The animals receiving the latter were divided into groups fed either ad libitum, or pair-fed, on a calorie basis, with the chow-fed animals. Half of the animals were submitted to a swimming program for 4 wk. Body weight, total and HDL CHOL were measured at the end of the treatments. Exercise-trained rats ingested the same amount of calories as their sedentary counterparts, while the animals fed with high-energy diet ate almost twice as many calories as the chow-fed groups. The sedentary animals fed the palatable diet had higher body weights than the chow-fed animals, and exercise prevented this weight increase. Exercise did not have any significant effect on serum total CHOL, but increased significantly the HDL/total CHOL ratio by 15% in the chow-fed animals. The palatable diet increased total CHOL, and decreased the HDL/total CHOL ratio in sedentary animals, whereas the ratio in their trained counterparts was comparable to that of the sedentary chow-fed group. Exercise can thus prevent both weight gain and a decrease in HDL/total CHOL ratio produced by a palatable, high-energy diet in the female rat.