Objective To study the effect of ultra-pulsed CO2 fractional laser combined with platelet-rich plasma in the treatment of scars after facial acne. Methods Eighty patients with facial acne scars admitted to the 909th Hospital/Dongnan Hospital of Xiamen University from January 2023 to January 2024 were randomly divided into two groups using a random number table. The control group (n =40) received simple ultra-pulsed CO2 fractional laser treatment, while the observation group (n =40) received ultra-pulsed CO2 fractional laser combined with platelet-rich plasma treatment. The clinical effcacy, scar condition, p38MAPK pathway protein level, inflammatory indicators, and incidence of complications were compared between the two groups. Results The total effective rate of the observation group was 97.50%, which was higher than 80.00% of the control group (P <0.05). After treatment, the levels of MEK1, MEK2, ERK1, ERK2, INF-γ, IL-6 and IL-8 in the observation group were lower than those in the control group (P <0.05). The incidence of complications in the observation group was lower than that in the control group (P <0.05). Conclusion Ultra-pulsed CO2 fractional laser combined with platelet-rich plasma has a good effect in the treatment of patients with facial acne scars, which can effectively improve the scar condition, reduce the level of inflammatory factors, and has high safety.