Background and aim: The black seed belongs to Ranunculaceaes and has been used as a spice and a curative remedy for numerous disorders. With regard to the effect of this plant on infertility this study was designed to investigate the role of the hydro-alcoholic extract of black seed on gonadotropin, estrogen, progesterone and folliculogenesis in mice.Methods: In this experimental study, 40 mice were randomly divided in to 5 groups of 8 animals. (3 experimental groups, one control group and one placebo group). All mice received one dose of Cloprostenol (i.p) and after three days progesterone (s.c.) for menstrual synchronization. Placebo group received normal saline and three other experimental groups received 50, 100 and 200 mg/kg Nigella sativa extract (i.p.), every other day for to days. After 10 injections, blood samples were taken from all groups and hormonal measurements, including LH, FSH, estrogen, progesterone were measured by RIA technique. Ovaries were taken out and used for tissue slicing and then were studied using light microscope. Results were analyzed using ANOVA and Donkey tests.Results: Results showed a significant decrease in the level of FSH and LH. In addition, a significance increase was observed in the level of estrogen in all groups, while the level of progesterone was increased in the second experimental group (100 mg/kg extract groups). The third experimental group (200 mg/kg) showed a significant increase in the weight of ovaries and the number of follicles. The number of corpus luteum was significantly increased in second experimental group (100 mg/kg).Conclusion: The hydro-alcoholic extract of Nigella sativa may enhance the number of follicle and corpus luteum which can have positive effect on fertility in female mice.