To investigate the clinical effect of large-capacity compound microemulsion combined with microneedle introduction in the treatment of chloasma. Methods A total of 60 patients with chloasma who were treated in Haikou Red Fashion Medical Cosmetic Hospital, Liuzhou Meijia Medical Cosmetology Clinic and Guangzhou Zixin Plastic Surgery Hospital from January to July 2022 were randomly divided into control group and observation group, with 30 patients in each group. The control group was treated with 5 ml microemulsion combined with microneedle introduction, and the observation group was treated with 55 ml microemulsion combined with microneedle introduction. The clinical efficacy, MASI score and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 93.33%, which was higher than 70.00% in the control group, and the difference was statistically significant (P <0.05). The MASI scores of the observation group at 1,3 and 6 months after treatment were lower than those of the control group, and the differences were statistically significant (P <0.05). There was no significant difference in the incidence of adverse reactions such as facial pain, redness, itching, and increased pigmentation between the two groups (P >0.05). Conclusion The clinical efficacy of large-capacity compound microemulsion combined with microneedle introduction in the treatment of chloasma is ideal, which can effectively dilute plaque, improve skin quality, improve skin whiteness, and the incidence of adverse reactions is low . The clinical efficacy and safety are good.