The objectives of this study were: 1) to evaluate the effects of a fructose enriched diet (FED) on rat sperm quality, epididymal function (i.e. oxidative stress and alpha-glucosidase expression) and testosterone concentrations; 2) to determine if the administration of ghrelin (Ghrl), reverses the effects induced by FED. After validating the protocol as an inductor of metabolic syndrome like-symptoms, adult male rats were assigned to one of the following treatments for 8 weeks: FED ¼ 10% fructose enriched in water (v/v); FED þ Ghrl ¼ fructose enriched diet plus Ghrl (6 nmol/animal/day, s.c.) from week 6-8; or C ¼ water without fructose (n ¼ 5-10 animals/group). FED significantly decreased sperm concentration and motile sperm count/ml vs C (FED: 19.0 AE 1.6 Â 10 6 sperm/ml and 834.6 AE 137.0, respectively vs C: 25.8 AE 2.8 Â 10 6 and 1300.4 AE 202.4, respectively; p < 0.05); ghrelin injection reversed this negative effect (23.5 AE 1.6 Â 10 6 sperm/ml and 1381.7 AE 71.3 respectively). FED resulted in hypogonadism, but Ghrl could not normalize testosterone concentrations (C: 1.4 AE 0.1 ng/ml vs FED: 0.8 AE 0.2 ng/ml and FED þ Ghrl: 0.6 AE 0.2 ng/ml; p < 0.05). Ghrelin did not reverse metabolic abnormalities secondary to FED. FED did not alter epididymal expression of antioxidants enzymes (superoxido-dismutase, catalase and glutathione peroxidases-Gpx-). Nevertheless, FED þ Ghrl significantly increased the expression of Gpx3 (FED þ Ghrl: 3.47 AE 0.48 vs FED: 0.69 AE 0.28 and C: 1.00 AE 0.14; p < 0.05). The expression of neutral alpha-glucosidase, which is a marker of epididymal function, did not differ between treatments. In conclusion, the administration of Ghrl modulated the negative effects of FED on sperm quality, possibly by an epididymal increase in Gpx3 expression. However, Ghrl could not neither normalize the metabolism of FED animals, nor reverse hypogonadism.