Due to the positive affect of the training on the improvement of MS, "the effect of the comprehensive training on neurotrophin- 4/5 and other variables in women with MS" was investigated. Experimental groups (A, B, and C) performed their intervention. Based on the level of disability, different training was used. Control groups (A, B, and C) received only stretch training. At first, all pre-tests were performed and then the experimental groups performed their exercises during 12 weeks. At the end, depended variables were measured and ANCOVA was used. According to the results, showed that rehabilitation protocol has no effect on the levels of neurotrophin 4/5 in MS patients at levels A and C (P=0.504 and P=0.083) but significant increase observed in B level (P=0.010). The results also showed that at level A: BMI, fat percentage, speed and VO2max, and at level B: weight, BMI, fat percentage, endurance, dynamic balance, waist circumference, hip circumference, WHR and VO2max had a significant improvement. On the other hand, at level C, only BMI, fat percentage and VO2max were significantly improved. These results show that rehabilitation exercises have a positive effect on these variables and can increase the quality of life in these patients.