To investigate the pathologic characteristics of the articular cartilage and subchondral bone from osteoarthritic knees, and to compare the structural parameters of articular cartilage and subchondral bone between the medial and lateral tibial plateau, so as to determine the role of calcified zone and subchondral bone in the pathogenesis of osteoarthritis (OA). Methods The tibial plateaus were taken from 30 patients undergoing total knee arthroplasty between October 2009 and May 2011. The subjects included 11 males and 19 females with an average age of 65.1 years (range, 55-78years). The mean disease duration was 16.6 years (range, 10-25 years); the mean varus angle of the diseased knee was 9.3° (range, 1-23°). After gross observation, the cartilage-bone samples were taken out from the most weight-bearing regions in the internal areas of the medial and lateral plateaus. The decalcified paraffin-embedded sections were prepared and stained with HE and Safranin O/fast green for cartilage assessment (Mankin score), staging, and bone histomorphometry; the pathologic features of the cartilage and subchondral bone were also observed. The thickness of total articular cartilage (TAC), articular calcified cartilage (ACC), subchondral bone plate (SCP), and the trabecular bone volume (BV/TV) were measured by Image Pro Plus 6.0 imaging system, then the ratio of ACC/TAC was calculated. Results Macroscopic results showed that articular cartilage degeneration was more severe in the medial plateau than in the lateral plateau; Mankin score of the medial plateau (12.4 ± 1.1) was significantly higher than that of the lateral plateau (8.3 ± 1.6) (t=12.173, P=0.000). In the 60 samples, 14 samples were at stage I, characterisd by fissures within the superficial zone, dupl icated tidemark, and thickend subchondral bone; 19 samples were at stage II, characterisd by fissures extending into the deep zone, multiple subchondral bone resorption pits, and obviously thickend subchondral bone; and 27 samples were at stage III, characterisd by full-thickness cartilage defects, endochondral ossification, and eburnated subchondral bone. The bone histomorphometric study showed that TAC thickness of the medial plateau was significantly lower than that of the lateral plateau (P lt; 0.05); the ratios of ACC/TAC, BV/TV, and SCP thickness of the medial plateau were significantly higher than those of the lateral plateau (P lt; 0.05). However, there was no significantdifference in the ACC thickness between the medial and lateral plateaus (P gt; 0.05). Conclusion The calcified zone andsubchondral bone may play an important role in the initiation and progression of OA.