Abstract: Objective To assess the effect of ascorbic acid/ferric chloride (AA/FeCl3) in attenuating cartilage damage in rats with osteoarthritis. Methods Thirty adult male Wistar rats with surgically induced osteoarthritis were randomized into 2 groups for treatment with intra-articular injection of saline (control group) or AA/FeCl3 mixture (AA group) once a week starting from the third week after the operation. At 6, 9, and 12 weeks after the operation, 5 rats from each group were sacrificed for observing subchondral bone changes on X-ray films and evaluation of cartilage degeneration in the right knee joints using safranin-O/Fast green staining and a modified OARSI scoring system. The degradation of the cartilage matrix was observed by immunohistochemical staining for type II collagen. Results X-ray examination in saline control group revealed the presence of osteophytes and narrowing of the joint space at 9 weeks, and the joint line disappeared at 12 weeks after the surgery; only slight irregularity of the articular surface was observed in the AA group at 9 and 12 weeks. OARSI scores were significantly lower in AA group than in the control group at 9 weeks (18.67±0.67 vs 12.17±2.75; P<0.05) and 12 weeks (20.11±1.84 vs 13.77± 0.40; P<0.05) but not at 6 weeks after the surgery. The content of type 2 collagen in AA group was significantly higher than that in the control group at 6 weeks (0.36±0.039 vs 0.49±0.029; P<0.05) and 9 weeks after the surgery (0.25±0.041 vs 0.38±0.040; P< 0.05). Conclusions Early intra-articular injection of AA/FeCl3 can effectively delay the progression of post-traumatic osteoarthritis in rats.