The present invention relates to anti-inflammatory activity of eggshell membrane, processed eggshell membrane preparations and eggshell membrane isolates. The invention is directed to eggshell membrane compositions exhibiting anti-inflammatory activity as measured by effects on down-regulating pro-inflammatory plasma antigens in mammals that had orally ingested such compositions. This information supports the potential benefits from administration of naturally occurring material found in eggshell membrane, processed eggshell membrane, eggshell membrane isolates and combinations to reduce pain and inflammation associated with arthritis and other inflammatory conditions.