Acne vulgaris (AV) is an inflammatory disease of skin on the follicle polisebasea frequent and considered dermatological problems the most common worldwide. This study investigates the relationship topical therapy using autologous serum containing doxycycline in women with moderate to severe acne vulgaris. Research conducted in Makassar, South Sulawesi, as many as 13 samples that met the inclusion criteria. Clinical examination in patients with moderate acne vulgaris to severe and based on clinical manifestations, level of sebum measured before, and levels of estradiol. All patients given the autologous serum after being given doxycycline 200 mg single dose oral which will be applied every night. Furthermore monitored on day to 14 and day to 28. The data were processed using paired Wilcoxon test. Results improvement in clinical manifestations and levels of sebum on days 14 and 28 compared to day 1 was significantly (p <0.05). There were improvements in clinical manifestations and decrease sebum levels in patients with moderate to severe AV after application of autologous serum containing doxycycline.