Objective To compare the changes in reproductive and developmental indexes after administration of different doses of cyclophosphamide before mating in Sprague Dawley ( SD) female rats, and to establish a standardized positive model for fertility and early embryo developmental toxicity test (Phase I). Methods One hundred and fifty SD rats (75 male, 75 female) were randomly divided into three groups ( n = 50; 25 male, 25 female), solvent control, cyclophosphamide 100 mg / kg and cyclophosphamide 20 mg / kg. Female rats were injected intraperitoneally with 20 mg / kg or 100 mg / kg of cyclophosphamide once daily in the 14 days preceding the mating period.The solvent control group was given the same volume of normal saline via the same route. Drug was administered from 14 days before mating until the 7th day of gestation (GD₇, the day found the sperm orthe pudendal embolism seemed as GD₀ ). No drug was administered to male rats in any group. General physical examinationof the animals was performed daily, body weight was measured twice a week and food intake was measured once a week. Female rats were sacrificed at GD₁₄ and pregnancy outcomes including pregnancy rate, loss rate before implantation, rate of implantation, the numbers of corpora lutea, loss rate after implantation, live fetuses, rate of live fetuses, uterine plus fetal weight and rate of absorbed fetuses were recorded. Results Compared with the solvent control group, the body weight and food intake of the two cyclophosphamide groups were all significantly decreased (P<0. 05 and P<0. 01).There was no significant difference in pregnancy, pre-implantation loss and implantation rates, or the average number of corpora lutea and the mean implantation number.The weight of uterus plus fetuses in the cyclophosphamide 20 mg / kggroup was significantly reduced (P<0. 01). The average number of live fetuses, the rate of live fetuses, and uterus plus fetuses weight were significantly reduced, and the rate of absorbed fetuses was significantly higher in both treatment groups compared with the control group (P<0. 05 and P<0. 01). Conclusions One hundred milligrams per kilogram and 20 mg / kg of cyclophosphamide administered intraperitoneally to female rats once and 5 times a day during the 14 days preceding mating, can successfully establish a standardized positive model for fertility and early embryo developmental toxicity in SD female rats, with 20 mg / kg cyclophosphamide representing the best option.