Objective To investigate the effect of water light injection combined with intensive pulsed light in the treatment of female delayed acne and its effect on serum inflammation level. Methods From February 2022 to January 2024, 120 female patients with late onset acne in our hospital were selected and divided into observation group (n =60) and control group (n =60) according to the principle of random number table method. The control group was treated with intensive pulsed light alone, and the observation group was treated with water light injection combined with intensive pulsed light. The clinical efficacy, serum inflammatory factors [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 95.00%, which was higher than 80.00% in the control group (P <0.05). After 3 months of treatment, serum hs-CRP, IL-6 and TNF-α in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the observation group and the control group (P >0.05). Conclusion For female patients with late onset acne, the method of water light injection combined with intensive pulsed light has a good therapeutic effect, which can reduce the level of serum inflammatory factors, and does not increase the incidence of adverse reactions, with higher application safety.