Objective To explore the clinical effect of micro needle mesotherapy combined with ultra-picosecond laser in the treatment of chloasma. Methods A total of 50 patients with chloasma admitted to Xinjiang Wancheng Medical Cosmetic Clinic from June 2022 to February 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 25 patients in each group. The control group was treated with micro needle mesotherapy, and the observation group was treated with micro needle mesotherapy combined with ultra-picosecond laser. The clinical efficacy, skin lesion area, skin lesion color and skin disease quality of life score were compared between the two groups. Results The total e?ective rate of treatment in the observation group was 96.00%, which was higher than 76.00% in the control group, and the difference was statistically significant (P<0.05). After treatment, the skin lesion area, skin lesion color and DLQI score of the observation group were better than those of the control group, and the di?erences were statistically signifcant (P<0.05). Conclusion The clinical e?ect of micro needle mesotherapy combined with ultra-picosecond laser in the treatment of chloasma is good, which can effectively reduce the area of skin lesions, reduce the color of skin lesions, promote recovery, and improve the quality of life of patients.