Objective To observe the effects of notoginsenoside, Panax notoginseng flavonoids (PNF) , Panax notoginseng acid (PNA) , and their mixtures on the expressions of tissue factor (TF) and tissue factor pathway inhibitor 2 (TFPI-2) in rat endometriaum with whole cycle exogenous estrogen inter- vention. Methods Totally 160 female impuberty rats were randomly divided into the blank group (n =40) and the model group (n =120). Rats in the blank group were administered with normal saline by gastroga- vage for 3 weeks, while those in the model group were administered with estradiol valerate suspension. The two interventions lasted for 3 consecutive weeks. After 3 weeks of intervention, rats with asexual cycle were randomly divided into six groups, i.e., the model group, the continuous estrogen group, the No- toginsenoside group, the PNF group, the PNA group, the mixture group. Rats in the model group, the continuous estrogen group, the Notoginsenoside group, the PNF group, the PNA group, the mixture group were respectively administered with normal saline, estrogen, notoginsenoside, PNF, PNA, and mixture of effective Panax notoginseng fractions by gastrogavage for 2 successive weeks. Expression levels of TF, TFPI-2, TF mRNA, and TFPI-2 mRNA in the endometrium were detected 2 weeks later. Re-sults Compared with the blank group, positive expressions of TF and TF mRNA increased, and positive expressions of TFPI-2 and TFPI-2 mRNA decreased in the model group (P <0. 05, P <0. 01). Compared with the model group, the expressions of TF and TF mRNA significantly increased, the expressions of TF- PI-2 and TFPI-2 mRNA significantly decreased in the estrogen group at the end of the 5th week (P < 0. 01). Compared with the model group and the estrogen group, positive expressions of TF and TF mRNA significantly decreased, positive expressions of TFPI-2 and TFPI-2 mRNA significantly increased in the Notoginsenoside group, the PNF group, the PNA group, the mixture group (P <0. 05, P <0. 01). Com- pared with the Notoginsenoside group, positive expressions of TFPI-2 and TFPI-2 mRNA significantly in- creased in the mixture group (P <0. 05). Compared with the PNF group, the expressions of TF and TF mRNA significantly decreased in the Notoginsenoside group and the mixture group (P <0. 01) ; positive expressions of TFPI-2 increased in the mixture group (P <0. 05, P <0. 01). Conclusions The effective fractions of Panax notoginseng could decrease the-expression of TF and increase the expression of TFPI- 2 in rat endometrium with whole cycle exogenous estrogen intervention. They activated blood circulation and arrested bleeding possibly through inhibiting TF, blocking activation of coagulation system, and re- ducing inflammatory response. Meanwhile, it also could strengthen endometrial extracellular matrix, maintain the endometrial stability, thereby reducing endometrial disintegration and bleeding, and being beneficial for endometrium repairing and remodeling.