Abstract: In order to enhance the extraction yield of active substance from squid (Ommastrephes bartrami) melamin, the effect of ultrasonic on the physical structure and composition of squid melanin was studied. The ultrasonic power, intermission time, work time and total time were 15 W/mL, 1 second, 2 seconds and 20 minutes, respectively. The results showed that the characteristic absorption peak of 224 nm, 267 nm of the treated squid melanin became more prominent than those of untreated squid melanin in ultraviolet optical absorption spectrum. The data showed that the solubility of melanin enhanced significantly. Meanwhile, there was no new chemical substance in the treated melanin. The content of protein in melanin did not change obviously, but the lipid did. The amount of metals decreased obviously such as Ca, Mg, Na, K, Fe, Cu, Cd and Pb. The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) suggested that the squid melanin microspheres blasted during ultrasonic process. The uppermost change of squid melanin induced by ultrasonic only was the physical structure. There were more scraps and smaller balls in the squid melanin sample，which was treated by ultrasonic. This indicated that the ultrasonic might be an effective physical method to extract active substance from the squid melanin without breakage on the chemical structure.