To date, no study has been conducted to explore the bioactivity of the crinoid Comanthus bennetti. Here we report the anti-inflammatory properties of comaparvin (5,8-dihydroxy-10-methoxy-2-propylbenzo[h]chromen-4-one) based on in vivo experiments. Our preliminary screening for anti-inflammatory activity revealed that the crude extract of Comanthus bennetti significantly inhibited the expression of pro-inflammatory proteins in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Comaparvin isolated from crinoids significantly decreased the expression of inducible nitric oxide synthase (iNOS) protein and mRNA in LPS-stimulated macrophage cells. Moreover, our results showed that post-treatment with comaparvin significantly inhibited mechanical allodynia, thermal hyperalgesia and weight-bearing deficits in rats with carrageenan-induced inflammation. Comaparvin also attenuated leukocyte infiltration and iNOS protein expression in carrageenan-induced inflamed paws. These results suggest that comaparvin is a potential anti-inflammatory therapeutic agent against inflammatory pain.