Objective To study the clinical effect of picosecond laser combined with microneedle introduction of tranexamic acid in the treatment of chloasma. Methods A total of 64 patients with chloasma admitted to the Department of Cosmetic Dermatology, Shanghai Rose Medical Beauty Hospital from June 2022 to May 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 32 patients in each group. The control group was treated with picosecond laser, and the observation group was treated with picosecond laser combined with microneedle introduction of tranexamic acid. The Melasma Area Severity Index, clinical efficacy, adverse emotions and adverse reactions were compared between the two groups. Results The scores of Melasma Area Severity Index in the observation group were lower than those in the control group after treatment (P <0.05). The total effective rate of treatment in the observation group was 96.88%, which was higher than 78.13% in the control group (P <0.05). After treatment, the scores of anxiety and depression in the observation group were lower than those in the control group (P <0.05). The incidence of adverse reactions in the observation group was lower than that in the control group (P <0.05). Conclusion Picosecond laser combined with microneedle introduction of tranexamic acid in the treatment of chloasma has a good clinical effect, which can effectively alleviate the clinical symptoms of patients, improve the adverse emotions, and the incidence of adverse reactions is low. It is a safe and effective treatment plan.