Objective:To observe the clinical efficacy of Guizhi Fuling Pills combined with levonorgestrel intrauterine system (IUS) in the treatment of uterine adenomyosis and the effects on the levels of vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) in serum. MethodsA total of 108 patients with uterine adenomyosis were randomly assigned into treatment group and control group, 54 patients in each group. The control group was given levonorgestrel IUS, and the treatment group was treated with Guizhi Fuling Pills and levonorgestrel IUS. The course of treatment was 6 months. The clinical efficacy and safety were observed. The changes in endometrial thickness, uterine volume, dysmenorrhea score, menstrual volume score, serum sex hormone index [luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E,2,) ] and the levels of VEGF and CA125 were compared.  Results:①The total effective rate was 90.74% and 75.93% in the treatment group and the control group, respectively. The clinical efficacy in the treatment group was significantly superior to that in the control group (P,<,0.05). ②After treatment, the endometrial thickness, uterine volume, dysmenorrhea score and menstrual volume score were significantly lower in the treatment group than in the control group (P,<,0.05). ③After treatment, the levels of LH, FSH, VEGF and CA125 were significantly lower in the treatment group than in the control group (P,<,0.05), while the E,2, level was significantly higher than in the control group (P,<,0.05). ④The incidence of adverse reactions were 14.81% and 11.11% in the treatment group and the control group, respectively, with no significant difference between the groups (P,<,0.05).  Conclusion:In the treatment of uterine adenomyosis, Guizhi Fuling Pills combined with levonorgestrel IUS can more effectively improve the symptoms of dysmenorrhea and menorrhagia, reduce the uterine volume and endometrial thickness, and lower the levels of serum VEGF and CA125, resulting in better overall efficacy without increasing adverse reactions.