Objective To observe the mechanism of Penning Granule ( PG) for treating chronic endometritis (CE). Methods Totally 38 CE patients in line with inclusive criteria were assigned to the PG group (23 cases) and the control group (15 cases) according to random digit table. PG (consisting of sargentgloryvine stem, Herba Patriniae, Hedyotis Diffusa, red peony root, Angelica Sinensis, prepared mastiche, prepared myrrh, common burreed tuber, zedoary root, Spina Gleditsiae, Danshen root, Radix Bupleuri, asarum , Astragalus, Pangolin) was administered to patients in the PG group, 105 g each time, twice per day for 4 successive weeks. Those in the control group took Levofloxacin (0.5 g, once per day) and Metronidazole Tablet (0. 5 g, twice daily for 1 successive week). They were followed-up for half a year after ending treatment. The morphological changes of uterine endometrium were observed by hyst- eroscopy before and after treatment, and endometrium biopsy performed at fixed position. The expres- sions of mucin-1 (MUC-1 ) and hypoxia induced facter-1 α (HIF-1α) in inflammatory endometrium were analyzed. The clinical effects were compared between PG and antibiotics from improvement of clinical symptoms, hysteroscopic manifestations, pathological analyses, and molecular levels. Results The markedly effective rate of clinical symptoms in the PG group was 91. 3% (21/23) , higher than that of the control group [60. 0% (9/15) ; P <-0. 05]. The plasma cell CD38 infiltration in endometrial stroma of the PG group were significantly decreased, showing better effect than antibiotics in the control group (P < 0.05). The positive expression of MUC-1 was increased and the expression of HIF-1 α was decreased in the PG group, showing better effect than antibiotics in the control group (P <0. 05). Conclusion PG showed obvious effects for treating chronic endometritis , and it was superior to that of antibiotics alone.