Objective：To investigate the clinical efficacy of intra-articular injection of chitosan combined with low-dose corticosteroids in the treatment of knee osteoarthritis（KOA）in the early and middle stages. Methods：A retrospective analysis was conducted on 164 patients with KOA who visited and were followed up at the outpatient department of orthopedics at the First Affiliated Hospital of Nanjing Medical University from June 2021 to December 2022. Based on the treatment methods，patients were divided into three groups：Group A（control group，oral administration）consisted of 55 patients，Group B（intra -articular injection of chitosan+oral administration）had 53 patients，Group C（intra-articular injection of chitosan combined with low-dose glucocorticoids） included 56 patients. Variations in pain visual analogue scale（VAS），Lysholm score，Hospital for Special Surgery（HSS）score，and the levels of inflammatory cytokines in the synovial fluid（interleukin-1，IL-1；interleukin-6，IL-6；tumor necrosis factor-alpha，TNF-α） were compared before and after treatment. Clinical efficacy was also evaluated. Results：All cases were followed up for 7-12 months and no cases were lost. Post-treatment VAS scores，Lysholm scores，HSS scores，and the levels of synovial fluid inflammatory cytokines （IL-1，IL-6，and TNF-α）were all significantly improved compared to pre-treatment levels in each group（P ＜0.05）. There were no significant differences in pre-treatment VAS scores，Lysholm scores，HSS scores and the levels of IL-1，IL-6，and TNF-α among the three groups（P ＞ 0.05）；however，post-treatment comparisons showed significant differences（P ＜0.05）. Compared with each other， Group C showed better outcomes than Groups A and B，and Group B was superior to Group A，with significant statistical differences （P ＜0.05）.The comparison of clinical efficacy among the three groups also showed statistically significant differences（P ＜0.05）. Conclusion：Intra-articular injection of chitosan combined with low-dose corticosteroids shows significant clinical efficacy in the treatment of KOA in early and middle stages，with the advantages of minimal trauma，rapid onset，lasting efficacy and avoids the adverse reactions of external application or oral administration of non-steroidal anti-inflammatory drugs. As a first-line treatment option，its clinical promotion and use are recommended.