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This study evaluated the effect of oral glucosamine and intramuscular injection (IM) of snail mucin on the progression of experimental osteoarthritis (OA) in dogs. Twenty adult mongrels with mean body weight (12.4±1.8 kg) were used. Experimental OA was induced surgically using the groove model. The dogs were randomly divided into three groups following radiographic evidence of OA. Group one (control) comprised of ten dogs treated with normal saline twice weekly for four weeks following OA. Group two comprised of five dogs treated with 10mg/kg of oral glucosamine daily for four weeks. Group three comprised of five dogs treated with 5mg/kg intramuscular injection of 5% solution of snail mucin twice weekly for four weeks. Blood was obtained from the cephalic vein before surgical arthrotomy, after surgical arthrotomy, immediately after radiographic confirmation of OA (Week 0) and at two weeks interval up to 4 weeks of treatment. Efficacy of the drugs was assessed by changes in plasma IL-6 and MMP-3, while safety was determined using the changes in packed cell volume (PCV), total white blood cell counts (WBC) and observable adverse reactions associated with the administration of the drugs. In this study, the PCV and WBC did not differ significantly (P> 0.05) from the control group. Plasma IL-6 and MMP-3 were significantly (P< 0.05) lower both in glucosamine-treated and snail mucin-treated dogs up to week 4 of treatment when compared with the control group. However, there were no significant (P > 0.05) differences in IL-6 and MMP-3 between the two treatment groups. In addition, painful swelling at the site of injection was observed in dogs treated with snail mucin, while no adverse reaction was observed in dogs treated with oral glucosamine. It was therefore concluded that both oral glucosamine and IM injection of snail mucin comparably modified the progression of OA. However, owing to the adverse reaction noted with IM injection of snail mucin, further study is required to determine the most appropriate route of administration. [ABSTRACT FROM AUTHOR]