Hyaluronan and cortisone have controversial and an important role in the healing of degenerative osteoarthritis. The purpose of the research was to compare individual and combined effects of hyaluronan and cortisone on the healing of degenerative osteoarthritis and to determine the serum malondialdehyde level as a lipid peroxidation marker. A rabbit model was used in which a degenerative osteoarthritis was created in the articular cartilage by resection of anterior cruciate ligament. The rabbits divided into three groups namely were injected with hyaluronan (group A) and cortisone (group B) at days 31, 38 and 45. Cortisone at day 31 and hyaluronan at days 38 and 45 were injected to the third group (group C). We obtained blood samples from each rabbit to determine the malondialdehyde levels at days 1, 30, and 52. At day 52, 21 rabbits were sacrificed. In biopsies obtained from treated and untreated knees articular cartilage degeneration was examined by light microscopy. Histopathologically the healing rate was significantly higher in group C than the other groups. Degeneration decreased 72% in group A, 52% in group B and 88% in group C at day 22. Malondialdehyde levels were 2.05 ± 0.37 in the control group, 1.94 ± 0.54 in group A, 1.98 ± 0.37 in group B and 1.55 ± 0.41 in goup C. The malondialdehyde levels of group A and B were less than the control group (statistically insignificant, p > 0.05). But, there were statistically significant values between control group and group C (p < 0.05). The results showed that the combination of cortisone and hyaluronan is the most effective in the treatment of cartilage degeneration in the course of the ostearthritis and the malondialdehyde levels are correlated with the severity of degeneration. © 2003 Tohoku University Medical Press.