Objective and design <p>We aimed to investigate potential lymphatic vessel abnormalities associated with rosacea and elucidate effective rosacea treatment mechanism using long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser (LPND).</p> Material or subjects <p>32 female BALB/c mice were used to established the rosacea-like inflammation model and LPND treatment model. Human lymphatic endothelial cells (HLECs) were used for in vitro studies.</p> Treatment <p>LL37 and/or LPND treatment.</p> Methods <p>Transcriptomic analyses and clinical observation were performed. Techniques such as Western blotting, immunofluorescence staining, flow cytometry, and clearance assays were employed to assess characteristics of lymphatic vessels. Statistical comparisons between two groups were conducted using Student’s t-test or the Mann–Whitney U test, while comparisons among more than two groups were analyzed using one-way or two-way analysis of variance (ANOVA).</p> Results <p>Individuals with rosacea exhibited lymphatic dysfunction and LPND treatment could alleviate rosacea-associated clinical edema. Comparative analyses of acute and chronic mouse models revealed lymphatic vessel dilation, reduced density, and impaired function in chronic rosacea-like inflammation. LPND treatment mitigated chronic rosacea-like inflammation by ameliorating lymphatic vessel abnormalities. In vitro experiments demonstrated that LPND attenuated LL-37-induced inflammatory responses in HLECs.</p> Conclusions <p>We elucidated the abnormalities of lymphatic vessels in rosacea and provided evidence supporting the targeted lymphatic vessel therapies.</p>