Objective To prepare a mouse model of asthenozoospermia ( AZS) with high sperm DNA fragmentation (SDF) using corticosterone (CORT) and sodium benzoate (NaB). Methods Fifty 3-week-old male ICR mice were divided randomly into CORT-treated (n = 30) and NaB-treated (n= 20) groups. The CORT group was further divided into the following six groups (n= 5 per group): high CORT (500 μg / mL), medium CORT (200 μg /mL), and low CORT (10 μg / mL) drinking water group, drinking water control group, CORT injection (40 mg / kg) group, and injection control group ( normal saline). The animals were modeled continuously for 50 d. Mice in the NaB group were further divided into four groups (n= 5 per group): high NaB (500 mg / kg), medium NaB (300 mg /kg), and low NaB ( 100 mg / kg) gavage groups, and control group ( normal saline). The animals were modeled continuously for 50 d. The physiological state of the mice in each group was observed and mass changes were recorded continuously. The sperm motility capacity and DNA fragmentation index (DFI) of the sperm were observed from the tail of the epididymis after the end of the modeling. Results The rate of mass change in the CORT-injection moding group showed a downward trend. There was no significant difference (P>0. 05) in the high NaB gavage group, and the rate of body mass change in the high NaB gavage group was significantly decreased compared with the control group(P<0. 05). The percentages of forward motility sperm were significantly decreased in the CORT injection group (P>0. 05) and the percentage in the high NaB gavage group (P<0. 05), compared with the control group. The DFI was increased in the CORT injection group compared with the control group, but the difference was not significant (P>0. 05), and the DFI in the high NaB gavage group was significantly increased compared with the control group (P<0. 05). Conclusions Intragastric gavage with NaB 500 mg / (kg·d) for 50 d is an ideal method for constructing an animal model of AZS with high SDF.