Objective:To analyze the inhibitory effect of genistein on matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) through inhibition of nuclear factor-kappa B (NF-κB ) activation.Methods: A total of 36 female mice were divided into six groups (n=6 in each group): control group (untreated mice), endometriosis mice group, and endometriosis mice groups administered with genistein at different doses (1.30 mg/day; 1.95 mg/day; 2.60 mg/day; and 3.25 mg/day). The genistein treatment was performed for 14 d. The expressions of NF-κB , MMP-2 and MMP-9 on the endometriosis lesions were analyzed by the immunohistochemical technique.Results: The activity of NF-κB in the endometriosis group increased significantly than that of the control group (P<0.05). The expression of MMP-2 or MMP-9 in the endometriosis group increased significantly than that of the control group (P<0.05). Administration of genistein at different doses was capable of significantly reducing the activity of NF-κB compared to that of the endometriosis group (P<0.05), reaching the level comparable to that of the control group at the third highest dose (P>0.05). The four doses of genistein administration were capable of significantly reducing the expression of MMP-2 compared to that of the endometriosis group (P<0.05), reaching an expression comparable to that of the control group for the highest dose (P>0.05). Administration of genistein at different doses was capable of significantly reducing the expression of MMP-9 compared to that of the endometriosis group (P<0.05), reaching the level comparable to that of the control group at the highest dose (P>0.05). Conclusions:Genistein suppresses the expression of MMP-2 and MMP-9 through suppressing NF-κB activity in the peritoneum of murine model of endometriosis.