Introduction: Main cause of the loss of joint function in septic arthritis is destruction of cartilage. Although intraarticular pressure can be decreased by both early antibiotic therapy and drainage, secondary changes occur in the joint. Synovectomy combined with conventional therapy brings benefit for preventing of destruction of cartilage. Osmic acid is a sclerosing agent used currently in late period chemical synovectomy. In our study we investigated that if chemical synovectomy with OsO4 contributes to the treatment in early period of septic arthritis as well as conventional therapy. Materials and Methods: In our study 55 white New Zealand rabbits' knee joints were used. Intraarticular 0.3 ml of serum physiologic (SP) was administered in control groups (Group 1 and 2). Experiments performed in four main groups as follows: In knee joints where septic atrhritis was formed, antibiotic lavage plus drainage (conventional tharepy) were used in Group 5 and 6; chemical synovectomy with osmic acid combined with conventional therapy in day 3 (Group 7 and 9) and in day 5 (Group 8 and 10). Effect of osmic acid on normal joint cartilage was also observed in non-infected knee joints (Group 3 and 4). Slices were cut from femoral condyl and tibia joint surfaces of knee joints exposed histological tissue process and staining and these slices were scored in light microscopy according to Salter's histological score method. Average score of all parameters and total average score indicating total destruction of cartilage were evaluated statistically by Kolmogorov-Smirnov 2-Sample Test. Results: Results obtained in tibia; 1. A statistical significant difference was found between Group 1 and 3 in terms of number of chondrocyte (p < 0.05). 2. There was a significant difference between Group 5 and 7 in terms of loss of orthrochromasy in extracellular matrix, formation of pannus, loss of surface matrix and total score (p < 0.05). 3. There was a significant difference between Group 6 and 8 in terms of total score (p < 0.05). Results obtained in femur; 4. There was a significant difference between Group 1 and 3 in terms of number of chondrocyte (p < 0.05) and total score (p < 0.01). 5. There was a significant difference between Group 5 and 7 in terms of loss of surface matrix and total score (p < 0.05). Discussion: In treatment of early period of septic arthritis OsO4 administration especially in day 5 was found to be effective in elimination of synovial membrane which can induce permanent damage. However, it was observed that OsO4 administration has a time-dependent effect on exacerbation of inflamation and formation of secondary complications. It was concluded that use of OsO4 in early period but as possible as after day 5 could reduce these complications.