Muscle-derived neurotrophins are thought to contribute to the adaptation of skeletal muscle to exercise. The NT-4/5 protein is one of the family members of neurotrophins that remains rather unknown compared to other members. The aim of this present study was to determine the effect of one session of resistance exercise on the levels of NT-4/5 protein in Soleus and Flexor HallucisLongus muscles of male wistar rats. 24 wistar rats (230±20g) were randomly assigned into two groups including (i) control group (N=8) and (ii) exercise group (N=16). In the exercise session, animals in 3 sets and 5 times climbed up a ladder while carrying 30% of their body weight. Animals of the exercise group were sacrificed 24 and 48 hours after exercise and their Soleus and Flexor HallucisLongus muscles were removed. The levels of NT-4/5 protein were measured using the Elisa kits. One-way ANOVA and independent T-test were used to analyze the obtained data. The results showed significant increases in NT-4/5 protein levels in the Soleus muscle at 24 and 48 h after resistance exercise whereas one session training did not significantly affect the levels of NT-4/5 protein in the FHL muscle. Since one session of resistance exercise resulted in changes in the levels of NT-4/5 protein, this exercise model may be considered as an appropriate model to stimulate the response of muscle-derived neurotrophin, especially in slow muscles.