A comparison of biomechanical and biochemical markers of muscle soleus and muscle gastrocnemius fatigue in rats for two days after 5 days of using antioxidant C60 fullerene (daily dose was 1 mg·kg-1) was performed. It was shown that its long-term use to increase muscle strength response against the background of muscle fatigue by 60-65 and 35-40% in slow and fast muscle, respectively. The residual effect of water-soluble C60 fullerene on slow muscle remains significant (20-25%) even after 2 days after discontinuation of the drug. At the same time, its residual effect on fast muscle on the 2nd day remains at a minimum level, which does not significantly increase muscle performance. Prolonged usage of water-soluble C60 fullerene helps to reduce oxidative processes by 30-40% in fast and by 21-25% in slow muscles by maintaining a balance between prooxidants and antioxidant defense system. A comparative analysis of oxidative stress markers and indicators of the state of antioxidant defense systems in fast and slow muscles showed that the residual therapeutic effect of water-soluble C60 fullerene after long-term use is 30-40% higher in muscle soleus than in muscle gastrocnemius. The obtained results demonstrate the long-term kinetics of water-soluble C60 fullerene excretion from the body, which contributes to long-term (at least two days) compensatory activation of the endogenous antioxidant system in response to muscle stimulation, which should be considered when developing new therapeutic drugs based on it.