OBJECTIVE： To study the effect of Zuogui pill on the expression of gap junction protein 43 （Cx43） in ovarian tissue of mice with premature ovarian failure （POF） induced by intraperitoneal injection of cyclophosphamide （CTX）， and explore its mechanism in the treatment of chemotherapy-induced POF. METHODS： 72 mice were randomly divided into blank group， model group， Estradiol valerate tablet group （positive control， 0.000 13 g/kg）， Zuogui pill low-dose， medium-dose， high-dose groups （13.65， 40.95， 122.85 g/kg） by body mass， 10 in each group. Except for blank group， other groups were reduce POF model by ip CTX， once a day， for 20 d. Meanwhile， the mice were intragastrically administrated related medicines， once a day， for 30 d. After 2 h of last administration， reverse transcription-polymerase chain reaction method and Western blot method were used to detect the Cx43 mRNA and protein expressions in ovarian tissue respectively， and immunohistochemistry method was adopted to detect the distribution of Cx43 protein in ovarian tissue. RESULTS： Compared with blank group， Cx43 mRNA and protein expressions in ovarian tissue of mice in model group were obviously weakened， and the distribution of Cx43 protein in follicle and granulocytes were obviously reduced （P＜0.01）. Compared with model group， Cx43 mRNA and protein expressions in ovarian tissue of mice in Estradiol valerate tablet group and Zuogui pill medium-dose， high-dose groups were obviously strengthened， and the distribution of Cx43 protein in follicle and granulocytes were obviously increased （P＜0.01）. CONCLUSIONS： Zuogui pill can increase the Cx43 mRNA and protein expressions in ovarian tissue of CTX-induced POF mice， increase the distribution of Cx43 in follicle and granulocytes and gap junction function， which may be one of the treatment mechanism of POF.