Objective To compare the effects of 5.0 mg/ml and 2.5 mg/ml hyaluronic acid mesotherapy on facial rejuvenation. Methods A total of 89 patients who received facial rejuvenation in our hospital from April 2022 to December 2023 were randomly divided into observation group (45 patients) and control group (44 patients). The control group was treated with 5.0 mg/ml hyaluronic acid for mesotherapy intervention, while the observation group was treated with 2.5 mg/ml hyaluronic acid for mesotherapy intervention. The skin status and adverse reactions of the two groups were compared. Results After intervention, the scores of wrinkles, pores and spots in the observation group were better than those in the control group (P <0.05). The incidence of adverse reactions in the observation group was 4.44%, which was lower than 22.73% in the control group (P <0.05). Conclusion 2.5 mg/ml hyaluronic acid mesotherapy can better improve wrinkles, pores, spots, etc., and can reduce the risk of adverse reactions, which is worthy of clinical application.