Introduction: Depomedroxyprogestron Acetate (DMPA) is one of the long-acting methods of Contraception. It is usually administered intramuscularly (150 mg) after every 3 months. Its efficacy is the same as IUD and sterilization, but problems of spotting and amenorrhea have been seen after dosage. During the first 6 months of use, it often leads the women to discontinue the treatment. So, we take a decision to find an absolute way of treatment of these problems to prevent the discontinuation of this contraception effective method.Materials and Methods: This clinical trial study was excersiced, in 2006-2007 in Zahedan, on the women in reproductive ages who were referred to obstetric clinics and had regular menstruation before receiving DMPA and abnormal uterine bleeding (AUB) such as; spotting or metrorrhagia after its use, selected and divided in two equal groups randomly. In first group, we prescribed oral conjugated estrogen 1/25 mg daily, and in second group, 150 mg intramuscular DMPA (its later dose) and work up our patients for two weeks. We used SPSS software and analyzed data by Chi square and t-test and considered significant differentiations if P-value was (p<0.05).Results: In 23 cases (58.9%) of patients treated with oral estrogen, AUB was stopped in average 5 days whereas in 33 cases (84.6%) of patients treated with the injection of later dose of DMPA, it stopped in average 2 days. So, their differentiation was significant (p<0.05).conclusion: Treatment of abnormal uterine bleeding (AUB) after injection of DMPA with the injection of its later dose is more effective than oral estrogen.