Sargassum horneri is an edible brown seaweed with potential anti-inflammatory properties. The present study was designed to evaluate the anti-inflammatory properties of S. horneri using an in vivo mouse asthma model following exposure to particulate matter (PM). 7-8 week old BALB/c mice (20-25 g) were randomly divided into seven groups (n = 4) as follows: 1: no treatment, 2: OVA (ovalbumin) + PM, 3: OVA + PM + SHE (S. horneri ethanol extract) 200 mg kg-1, 4: OVA + PM + SHE 400 mg kg-1, 5: OVA + PM + prednisone 5 mg kg-1, 6: OVA only, and 7: PM only. All mice (except healthy controls) were sensitized on the first day by intraperitoneal injection of 10 μg OVA and 2 mg Al(OH)3 in 200 μL of saline. Starting from day 15, mice (except groups 1 and 6) were exposed to sonicated PM (5 mg m-3, 30 min day-1) through a nebulizer daily for 7 consecutive days. Mice exposed to PM and OVA showed up-regulated expression of MAPKs and pro-inflammatory cytokine production in the lungs. Furthermore, PM-exposed lungs had significantly reduced expression of Nrf2 and HO-1 genes. However, oral administration of the SHE reduced the phosphorylation levels of MAPKs, iNOS and COX2 expression levels, and mRNA expression levels of pro-inflammatory cytokines. In addition, SHE treated group mice had up-regulated anti-oxidant gene expression levels in the lungs compared to group 2. These findings demonstrate that oral administration of the SHE re-establishes PM-induced inflammation and oxidative stress in the lungs. Taken together, the SHE has therapeutic potential in preventing PM-induced inflammation and oxidative stress.