Certain mangrove endophytic fungi have unique physiological mechanisms, such as anti-inflammatory properties. A new polyketone, namely N-acetoxyethyl-3-(3,5-dimethyl-1,3-heptadienyl)-5-chloro-7-methyl-7-acetoxy-6,8-(2H,7H)-isoquinolinedione (1), and 17 known compounds (2-18) were isolated from the mangrove endophytic fungus Diaporthe pseudooculi HHUF 30617. The structure of the new compound was elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionisation mass spectroscopy (HRESI-MS). The anti-inflammatory activities of the compounds were evaluated using the zebrafish migratory fluorescent cell count assay. The results suggest the potential of the above compounds for treating inflammation. These findings aid the development of natural marine products based on mangrove endophytic fungal metabolites to counter conditions such as copper toxicity.