Treatment of osteoporosis remains a therapeutic challenge. The effect of Apium Nodiflorum extract on development of experimental osteoporosis, pain thresholds and carrageenan-induced inflammation has been studied in ovariectomized osteoporotic Wistar rats. After osteoporosis verification rats were randomized and received vehicle only, HPLC-standardized Apium extract (equal to 2.4 mg/kg Quercetin) or Genistein (2.5 mg/kg) for 8 weeks. To verify the effect of Apium on the development of osteoporosis, bone mineral density (BMD) and bone mineral content (BMC), bone histology and plasma levels of IL-6 and RANKL were measured 6 months after ovariectomy and 8 weeks after treatment with Apium extract or Genistein as comparator. Inflammatory hyperalgesia was induced by intraplantar injection of 1% Carrageenan. Apium extract and Genistein impeded the development of osteoporosis (significant differences were shown for BMC and BMD levels in drug vs. vehicle treated rats) and improved bone histology and histological score. Apium and Genistein decreased IL-6 level. Both treatments alleviated mechanical hyperalgesia, decreased exudative reaction and lowered inflammatory pain threshold. The results suggested that Apium extract could be an alternative therapy for post-menopausal osteoporosis.