Cholesterol is also abundant in other subfractions of rabbit semen. Sperm membrane undergoes several modifications from the testis, were they are produced, to the female tract. Membrane lipids, especially chol, are responsible for changes in membrane fluidity and cell responsiveness to the environment, alterations involved in a series of physiological events that are unique for these cells. Chol efflux from PM leads to changes in membrane structure and fluidity that give rise to the sperm capacitated state. Capacitation is defined as the time-dependent acquisition of fertilization competence, ability acquired by the sperm during its transit through the female tract. This process involves a PKAregulated increase in tyrosine phosphorylation of a subset of proteins, and is generally assessed as the ability of the acrosome-intact sperm to undergo AR in response to physiological inducers such as the zona pellucida or progesterone. Animals fed with saturated fat-enriched diets raise their plasmatic chol levels and this would have impact on the cell-specific lipid equilibrium between chol and phospholipids that organize the PM. The later modification could affect cellular functions as signal transduction pathways coupled to membrane chol. Sperm membrane lipids are highly responsive to dietary manipulation. Chol-rich diets have been shown to produce a decrease in sperm AR kinetics, and detrimental effects on Leydig and Sertoli cell secretory capacity in rabbits. Moreover, previous works showed that human male infertility might be associated with altered lipid metabolism in seminal plasma. The present study aimed at investigating the effects of dietinduced hypercholesterolemia on rabbit semen and sperm physiology, membrane cholesterol concentration, cell motility, capacitation and acrosome reaction. Plasma chol level reported for rabbit ranges from 35–53 mg/dl according to Harkness and Wagner. However, we found that cholesterolemia from rabbits under control conditions maintained below that range all over the experimental CP-690550 period. On the other hand, it is widely known that saturated fat-enriched diets induce hypercholesterolemia in adult male rabbits. Accordingly, serum cholesterol level in HCR significantly increased at 45 days of ED diet. The measures determined for different semen parameters were in agreement with standard estimations. It is well known that diet lipids have consequences on sperm lipid composition. Animals treated with flaxseed or a-linolenic acid improves semen quality by modifying sperm lipid composition. On the other hand, feeding saturated fat rich diets had been shown to trigger detrimental effects over rabbit semen. In our results, ED diet did not affect semen parameters as pH and sperm viability. In previous results, high serum chol was associated with a decrease in sperm concentration and sperm motility. Our results confirm the reduction in sperm motility, although our experimental conditions differed in feeding time and fat intake. In contrast to previous work, we found that semen volume significantly decreased in HCR.