drastic acceleration of fibrillation of insulin by transient cavitation bubble amyloidfibril formation of proteins can be accelerated by ultrasonic irradiation to the peptide solutions although this phenomenon contributes to understanding pathogenic behavior of amyloidosis its physical mechanism has not been clarified because several factors cavitation temperature increase stirring effect and so on related to ultrasonic irradiation can participate in the fibrillation reaction here we independently study contributions of the possible factors using insulin which is extremely stable and then suitable for the mechanism clarification we find that the optimized ultrasonic irradiation can drastically accelerate the fibrillation reaction the time for completing the reaction is shortened compared with the highspeed 1200rpm stirring agitation by a factor of 430 the fibrillation reaction proceeds only when the subharmonicmode intensity exceeds a threshold indicating generation of the transient cavitation bubbles our results reveal that not the temperature increase but the transient cavitation bubbles work as the dominant accelerator of the fibrillation reaction