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Background: Intense pulsed light (IPL) has been widely used to improve cutaneous photoaging in recent years. Several studies began to explore the changes of skin barrier function after treatment, but the changes of skin surface lipids (SSL), especially specific lipid content and types are still unclear. Methods: A total of 25 female volunteers were included in our study, and each of them received three full-face treatments with one month apart. Before the first treatment and 1 month after the last treatment, we collected clinical photos and skin stratum corneum samples from individuals. A 5-level scale was used to evaluate the efficacy of IPL treatment, liquid chromatography-mass spectrometry (LC-MS), and Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA) were used to analyze the changes of SSL. Results: Two patients got no improvement after treatment, 6 patients had poor improvement and mild improvement was achieved in 9 patients, 5 and 3 patients reported moderate and significant improvement. The overall "effective" rate was 68 % and the "significant effective" rate was 32 %. The results showed 18 lipid subclasses and 487 lipid molecules were identified. The change of total lipid volume was not statistically significant (P = 0.088>0.05), but lipid subclass analysis showed the amount of Triglyceride (TG), Phosphatidic Acid (PA), Phosphatidylglycerol (PG) and Lysophosphatidylglycerol (LPG) were significantly increased (P < 0.05). There were 55 kinds of lipid molecules with significant difference after treatment (P < 0.05), and 51 of them belong to TG. The analysis of chain saturation of TG showed that the quantity of TG with 0, 1 and 2 unsaturated bonds increased significantly (P < 0.05). Conclusions: IPL treatment does not have a significant effect on the overall amount of lipids while the amount of TG, PA, PG, LPG were significantly increased. These lipid changes may potentially improve the skin barrier function, but more high-quality and comprehensive studies are still needed. Bullet Point: Lipidomics analysis based on LC-MS; Changes of skin surface lipid after IPL treatment; the relationships between skin surface lipid and skin barrier functions. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]