We would like to emphasize the differentiations of diagnosis and treatment between general uterine leiomyomas and diffuse uterine leiomyomatosis (DUL), which is a kind of extremely rare disease. Levonorgestrel-releasing intrauterine system (LNG-IUS) is an attainable option provided to treat DUL with cerebral thrombosis, as a feasible novel method. Case report: A 21-year-old female patient with DUL was due to cerebral venous thrombosis caused by oral contraceptives. The patient was persistently vaginal bleeding after decreasing intracranial pressure and anticoagulant therapy for 3 days. Subsequently, a hysteroscopic submucosal myomectomy was performed to restore the normal shape of the uterine cavity, and the placement of Mirena was given after surgery, which aimly played a good role in hemostasis, prevention of severe menorrhagia and reconstruction of endometrial function. Conclusion: This case report shows that, levonorgestrel-releasing intrauterine system (LNG-IUS) is efficient and secure to treat DUL after hysteroscopic surgery, and simultaneously does not increase the risk of venous thromboembolism (VTE).