Minoxidil (Mx) is a conventional drug for androgenetic alopecia, prevent hair loss and promote hair growth. The solubility of Mx was improved to increase skin permeability by chemical enhancement methods and only worked over the long term. In this study, a new ultrasound (US) contrast agent, albumin shelled microbubbles (MBs) which absorbed chitosan oligosaccharide lactate (COL) and Mx were created, and combined with US energy in water-phase to enhance hair growth and reduce the treatment period. COL and Mx grafted with MBs (1480 nm) are synthesized a self-assembled complex of COL-MBs (4150 nm) and Mx-COL-MBs (4500 nm) in diameter. The US was applied at 3 W/cm2 for 1 min, and combined with 0.3% Mx coated Mx-COL-MBs. Similar to the environment of scalp is on the mildly acidic side of the pH scale (pH of 4.5 to 5.5), Mx diffusion from US+Mx-COL-MB through the dialysis membrane was rapid at pH 4 than pH 7.4. In the in vitro Franz diffusion experiments, at 18 hours, the release rate of combining US with Mx-COL-MBs or MBs plus Mx resulted in 11.1 times 8.0 more the penetration and deposition of Mx than in group MBs alone. From animal study, at days 10 and 14, the growth rate in group US+Mx-COL-MBs had increased by 22.6% and 64.7%, and significant differences (p<0.05) were obvious between group US+Mx-COL-MBs and other four groups. US+Mx-COL-MB in water-phase reduce hair growth duration, and the diameter of the hair shaft and the hair follicle size were both increased without skin damage.