OBJECTIVE To investigate the effects of oral exposure to iron oxide nanoparticles(Fe_2O_3NPs) on the reproductive system of male rats. METHODS Forty male SD rats were randomly divided into control group and low, medium, high dose groups, 10 rats in each group, normal saline and 50, 100 and 200 mg/kg Fe_2O_3NPs suspension were given by gavage, respectively. The volume of gavage was 10 mL/kg for 28 days. The body weight was weighed every three days, and the body weight changes of rats were recorded. After intraperitoneal anesthesia with 10% chloral hydrate, the rats were sacrificed by cervical dislocation, and the testis and epididymis were collected. Weigh and calculate the testicular coefficient and epididymal coefficient, the pathological sections of rat testis were observed by hematoxylin-eosin staining, the number of epididymal sperm was counted under an optical microscope and the sperm deformity rate was calculated. The activities of acid phosphatase(ACP), alkaline phosphatase(AKP), lactate dehydrogenase(LDH) and γ-glutamyl transpeptidase(γ-GT), the activity of superoxide dismutase(SOD), and the contents of glutathione(GSH) and malondialdehyde(MDA) in rat testis homogenate were detected by kit method. RESULTS Compared with control group, there was no significant difference in body weight, testicular coefficient and epididymal coefficient in each dose group. In the medium and high dose groups, the arrangement of spermatogenic epithelium was disordered and spermatogenic cells decreased. The number of sperm in high dose group was decreased, and the sperm deformity rate in medium and high dose groups was increased(P<0.01). The activity of ACP in medium and high dose groups increased(P<0.05), and the activity of γ-GT decreased(P<0.01). There was no significant change in the activity of AKP and LDH in testicular homogenate of rats in each group(P>0.05). The level of GSH in medium dose group was increased(P<0.05), and the content of MDA in medium and high dose groups was increased(P<0.01). There was no significant difference in SOD activity among the groups(P>0.05). CONCLUSIONS Under the conditions of this experiment, Fe_2O_3NPs can cause damage to the structure of rat testicular tissue, reduce the number of sperm, increase the rate of sperm deformity, interfere with the activity of marker enzymes in testicular tissue and induce oxidative stress injury, which has a negative impact on the reproductive system of male rats.