Background: Osteoarthritis can impair muscle structure and function. Numerous methods may be helpful for its treatment, i.e., hyaluronic acid, cell therapy, and physical training. Objectives: The present study investigated the independent and combined effect of these three interventions on the quadriceps muscle fiber count in the rat model of knee osteoarthritis. Methods: Fifty four rats were randomly divided into groups, including; healthy-control, osteoarthritis- control, osteoarthritis-training, osteoarthritis-stem cell, osteoarthritis-hyaluronic acid, osteoarthritis-hyaluronic-stem cell, osteoarthritis-stem cell-training, osteoarthritis-hyaluronic acid-training, and osteoarthritis-stem cell-hyaluronic acid-training. The exercise training program consisted of 30 minutes of running on the treadmill with no slope at a speed of 16 m/min for the first week. Then, the duration progressively reached 50 minutes in the eighth week. Stem cells were extracted from bone marrow and injected into the injured joint. Hyaluronic acid was injected into the injured joint in three separate weeks and once a week. All animals were anesthetized 48 hours after the last training session and injections. The samples were removed and sent to the laboratory. All significant levels were considered as P < 0.05. Results: Osteoarthritis significantly decreased muscle fibers compared to healthy animals. Aerobic training, stem cell therapy, hyaluronic acid, the interaction of training and stem cell, and the interaction of training, stem cell therapy, and hyaluronic acid significantly increased muscle fiber count. Conclusions: Concurrent use of aerobic training, stem cell, and hyaluronic acid treatments had more effect than each intervention alone on enhancing the muscle fiber count in the rat model of knee osteoarthritis.