The purpose of this study was to determine the effect of one intra-articular injection of hyaluronan on chondrocyte death and metabolism in injured cartilage. Twenty-three 6-month-old rabbits received partial-thickness articular cartilage defects created on each medial femoral condyle. In order to examine the effect on articular cartilage surrounding iatrogenic cartilage lesions, which can occur during arthroscopic procedures, Study 1 was performed: in 14 rabbits both knees were immediately rinsed with 0.9% NaCl. Experimental knees were treated with hyaluronan. Six rabbits were sacrificed at 2 days; eight rabbits 3 months postoperatively. Histomorphometric analysis was used for studying cell death in cartilage next to the defect. In order to examine the effect on longer lasting lesions, more reflecting the clinical situation, Study 2 was performed: after 6 months knee joints of nine rabbits were (i) irrigated with 0.9% NaCl, (ii) treated with hyaluronan after irrigation with 0.9% NaCl, or (iii) sham-treated. After 7 days patellas were used to study the chondrocyte metabolism by measuring the [S-35]sulfate incorporation. Study 1: Two days postoperatively, in hyaluronan-treated cartilage the percentage of dead cells was 6.7%, which was significantly lower compared to 16.2% in saline-treated cartilage. After 3 months the percentages of dead cells in both groups were statistically similar. Study 2: Hyaluronan treatment resulted in significantly higher [S-35]sulfate incorporation compared to knees irrigated with 0.9% NaCl. These results suggest a potential role for hyaluronan in preventing cell death following articular cartilage injury. One injection of hyaluronan improved cartilage metabolism in knees with 6-month-old cartilage defects. (c) 2008 Orthopaedic Research Society