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This study is aiming to investigate the protective effect of glucosamine, risedronate (alone or in combination) on articular cartilage in experimental model of immobilized rat knee. Twenty-five adult male albino rats were divided into five groups (five rats each): control group, immobilized group, glucosamine-treated group, risedronate-treated group, and group treated by a combination of glucosamine and risedronate. The articular cartilage was obtained for histological, immunohistochemical and morphometric studies. The immobilized group showed manifestations of osteoarthritis in the form of significant decrease of articular cartilage thickness with surface erosions, shrunken chondrocytes with pyknotic nuclei and marked manifested fall of chondrocyte number. There was manifested reduction of collagen contents of the articular cartilage using Masson trichrome stain. Safranin O-Fast Green revealed low proteoglycan contents. The collagen type II was also declined. The manikin score was 7.8. Risedronate improved this manifestation slightly more than glucosamine, but combination of booth drugs caused significant improvement of the damaged articular cartilage caused by immobilization. Oral administration of glucosamine and risedronate improved the degenerative changes of rat knee articular cartilage that follow immobilization. This improvement was more remarkable when both drugs were used in combination.