Objective: Breast cancer-related lymphedema (BCRL) is a major sequela after surgery or radiotherarpy for breast cancer. Manual lymphatic drainage (MLD) is designed to reduce lymph swelling by facilitating lymphatic drainage. This study attempted to determine the histologic changes in the skin and subcutaneous layer, and the immediate effect of MLD in decreasing lymphedema using ultrasound imaging, which is the method used most commonly to eliminate BCRL. Design: A single-group experimental study. Methods: Five subjects who were diagnosed with hemiparetic upper extremity lymphedema more than six months after breast cancer surgery participated in the study. MLD was performed for 60 minutes in the order of the thorax, breast, axilla, and upper arm of the affected side. In order to determine the effect of MLD, ultrasound imaging and limb volume were assessed. Two measurement tools were used for asessing lymphedema thickness among the pretest, posttest, and 30-minute follow-up period. Results: Significant diferences in ultrasound imaging and upper limb volume were found between the affected side and non-affected side (p<0.05). On the affected side, although ultrasound imaging showed a significant decrease after MLD (p<0.05), there were no significant difference in upper limb volume when compared to the baseline. Conclusions: In this study, a significant decrease in lymphedema by MLD was demonstrated by ultrasound imaging, which is considered to be more useful in assessing histological changes than limb volume measurements. Further research on the protocol for eliminating lymphedema will be needed.