The effect of cordycepin (3'-deoxyadenosine) on inflammation-induced osteoporosis (IMO) was studied in this paper. After the rats were treated orally with cordycepin (20 mg/kg), serum osteocalcin (OC), homocysteine (HCY), C-terminal cross-linked telopeptides of collagen type I (CTX), maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), they were examined by ELISA or immunohistochemistry. The specimens from the liver were also processed for light microscopic examination. The IMO rats showed a significant increase in plasma CTX, MDA, PMN, IL-1β, TNF-α, and nitrate levels as well as a significant decrease in plasma OC. These changes were attenuated by cordycepin (20 mg/kg) supplementation in the IMO rats. Examination of the liver specimens revealed mononuclear cell infiltration in the portal areas in the IMO rats which was not detected in the cordycepin (20 mg/kg) rats. These results suggest that cordycepin may act as an anti-inflammatory agent in magnesium silicate-induced inflammation in osteoporosis.