The morphological aspects of Schistosoma mansoni adult worms recovered from albino mice fed on a cholesterol-rich diet compared to mice fed on a standard chow were investigated. After feeding on their respective diets for over a period of 5 months, mice were subcutaneously infected with c. 50 S. mansoni cercariae/mouse. Blood samples were obtained 1 day prior to experimental infections and 63 days later, when mice were euthanized by jugular section (hypovolaemic shock). Total cholesterol (TC) levels were determined. Recovered worms were stained with hydrochloric carmine, and preserved as whole-mounts for examination by bright-field and laser confocal microscopy. The infected mice fed on high-fat chow showed higher levels of serum lipoproteins than the infected mice fed on standard chow, except for very-low-density lipoprotein cholesterol (VLDL-c) and triglycerides (TG). In this experiment, worms from mice fed on a high-fat chow showed a greater percentage of morphological differentiation regarding supernumerary testes, seminal vesicle, and seminal receptacle. In mice of this group, the rate of oocyte laying in the ovary was much higher than in control females. The present results suggest that cholesterol could be actively involved in the modulation of cell signalling and reproduction, because the lobes contained fully developed oocytes in variable amounts, different from control males. The data presented here are the first to report the role of a cholesterol-rich diet affecting the development of S. mansoni worms.