Background: Understanding the nature and function of fungal exoantigens might lead to novel approaches in the treatment and prophylaxis of some infectious diseases. Septic arthritis represents a serious problem for medicine due to the high incidence rate and severe complications.Objective: The present study aimed at assessing the immunomodulatory effects of Trichophyton rubrum culture filtrate as a novel compound in experimental septic arthritis.Method:The septic arthritis was haematogenously induced in Sprague-Dawley rats by a single intravenous injection of 109 colony forming units of the human clinical isolate Staphylococcus aureus producing toxic shock syndrome toxin-1. Trichophyton rubrum culture filtrate at two different doses 20 and 40 mg/kg was administered intraperituneally two days after bacterial inoculation in the treatment groups and concurrently with the appearance of clinical signs in the patient groups. The administration of Trichophyton rubrum solution was continued every other day for 10 injections.Results:The clinical evaluation showed that Trichophyton rubrum-treated rats were significantly protected from disease development compared with untreated controls. This finding was correlated with results of radiological evaluation of the involved joints. Although, the inflammatory cell infiltration, cartilage/bone destruction and synovial hypertrophy had been decreased in the treatment groups in comparison with arthritic controls however, the histological changes were not significant in these two groups.Conclusion:It is possible that Trichophyton rubrum antigens may play a role in modulating the immune responses and would be efficient in septic arthritis treatment.