To observe the efficacy of leuprorelin acetate (LA) combined with high-intensity focused ultrasound (HIFU) for treating patients with adenomyosis (AM). Methods: According to the random number table method, 60 patients with AM were divided into two groups. 30 patients in the control group had received the treatment of HIFU, and 30 patients in the study group had received the treatment of LA combined with HIFU. The uterine volume, the lesion volume, the menstrual status, the ovarian function, the adverse reactions rate and the recurrence rate of AM of the patients were compared between the two groups. The levels of serum carbohydrate antigen 125 (CA125), prostaglandin 2 (PGF2α) and adiponectin of the patients in the two groups were detected. Results: The uterine volume, the lesion volume, the scores of dysmenorrheal and menstrual volume and the levels of CA125 and PGF2α of the patients in the two groups after treatment had decreased significantly (P<0.05), and which of the patients in the study group were significantly lower than those of the patients in the control group (P<0.05).The adiponectin level of the patients in the two groups after treatment had increased significantly (P<0.05), and which of the patients in the study group was significantly higher than that of the patients in the control group (P<0.05). The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) of the patients in the two groups after treatment had decreased significantly (P<0.05), and which of the patients in the study group were significantly lower than those of the patients in the control group (P<0.05). There were no significant differences in the total incidence of adverse reactions and the recurrence rate after 6 months of follow-up of the patients between the two groups (P>0.05). Conclusion: LA combined with HIFU for treating the patients with AM can alleviate their dysmenorrhea, improve their menstrual volume and ovarian function, reduce their uterine and lesion volumes, and which can regulate the serum CA125, PGF2α, and adiponectin levels of the patients, and without increasing the risk of their adverse reactions and their AM recurrence.