Objective:To evaluate whether low-frequency ultrasound-facilitated transdermal delivery of a Chinese medicine (CM) formula could improve the efficacy of intrapleural administration of interleukin-2 (IL-2)in treatment of malignant pleural effusion (MPE).Methods:A total of 110 eligible participants were randomized into the low-frequency sonophoresis (LFS) of CM (LSF/CM) group (55 cases) and the control group (55 cases) by simple randomization using a random number table.The control group was treated with an intrapleural administration of IL-2;and the LFS/CM group was treated with LFS of a CM gel formulation,combined with the same IL-2 injection as in the control group.The CM formula consisted of Semen Lepidii,Semen Sinapis,Ramulus Cinnamomi,Poriacocos,Herba Lycopi,and Radix Paeoniae Rubra.After 2-week treatment,the therapeutic outcome was determined by the change of the amount of MPE,which was evaluated by B-scan ultrasound and/or chest X-ray,and the change of quality of life (QOL) scores,which were evaluated by the Eastern Cooperative Oncology Group (ECOG) performance status.Results:A significantly higher objective remission rate (ORR) was obtained with intrapleural IL-2 plus LFS/CM than IL-2 treatment alone (P=0.049).In addition,more patients in the LFS/CM group than in the control group had an improved QOL score (P=0.048),and no patients in the LFS/CM group had a reduced QOL.Conclusion:LFS of CM formulation could effectively alleviate MPE and improve the QOL of cancer patients.