This study aimed to investigate the anti-inflammatory effects and underlying mechanisms of Hibiscus manihot L. seeds essential oil (HMSE) on acne in mice. The HMSE was extracted using a flash extraction method, and its chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). To evaluate the anti-inflammatory activity of HMSE, RAW 264.7 cells were exposed to various concentrations of HMSE (31.25, 62.5, 125, 250 and 500 μg/mL) in the presence of lipopolysaccharide (LPS, 1 000 ng/mL) for 24 h. Levels of tumour necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-1β in the culture supernatant were measured, and protein expressions of inducible nitric oxide synthase (iNOS), TNF-α, IL-6, and IL-1β were evaluated. In addition, an oleic acid-induced acne mouse model was established to evaluate the in vivo effects of HMSE. The severity of acne lesions was scored histopathologically, HE staining was performed to examine acne-associated histological changes, and laser Doppler imaging was used to measure dorsal skin blood flow. Levels of TNF-α, IL-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and IL-4 in skin tissues were also determined. The results showed that HMSE yield obtained by flash extraction was 23.02% ± 0.63%. GC-MS analysis detected 27 chemical components in HMSE, comprising fatty acids, fatty alcohols, ketones, and other substances. HMSE significantly reduced TNF-α, PGE2, IL-6, and IL-1β levels in RAW 264.7 cells (P < 0.05) and downregulated the protein expressions of iNOS, TNF-α, IL-6, and IL-1β (P < 0.05), demonstrating protective effects against LPS-induced macrophage inflammation model. In the acne mouse model, HMSE treatment substantially improved acne symptoms, reduced desquamation and erythema, decreased skin blood flow and capillary density, and reduced cutaneous inflammation. In conclusion, HMSE ameliorates acne in oleic acid-induced ICR mice by reducing levels of pro-inflammatory cytokines and improving local inflammatory responses.