Objective To investigate the potential application of high-frequency ultrasound in quantitative evaluation of photodynamic therapy (PDT) for port-wine stain (PWS). Methods A total of 60 patients with PWS were included in the study. High-frequency ultrasound were used to measure the thickness of the skin at the lesions (epidermis and dermis) of the PWS and the thickness of the normal skin at the corresponding locations, and the thickened thickness was calculated; In doppler mode the skin blood flow was evaluated and graded according to the Adler blood flow grade method. The patient took normalized photographs under the same shooting conditions before each treatment, and 1-3 scores were classified effective while 0 was classified invalid. Before the first treatment, the baseline including ages, genders and BMI, and the thickened thickness of skin lesions and the blood flow rating of lesions were compared between the effective group and the invalid group. The thickened thickness and blood flow of PWS lesions were compared among patients before and after treatment. Results After a photodynamic therapy, all patients and the with the effective group had significant differences in the thickened thickness of skin lesions and the blood flow rating of lesions before and after treatment (P＜0.05). For some patients with visual score of 0 (invalid group), there was no statistical difference in blood flow signals before and after treatment (P = 0.899), but the thickened thickness of skin lesions decreased from 0.39mm (0.21-0.79) to 0.31mm (0.17- 0.65), the difference was statistically significant (P < 0.001). Conclusion High-frequency ultrasound can sensitively reflect changes in skin thickness and blood flow of PWS compared to traditional visual scores.