Intramuscular application of botulinum toxin (BoNT) is used as a successful therapy of muscle spasticity. Clinical practice shows, that even with the use of special guidance techniques to increase accuracy of targeting, BoNT may spread to adjacent sites by diffusion. This causes fluctuating treatment response, unintended side effects, and decrease of effect due to production of antibodies. Hence, clinicians require increase of efficacy and safety by dose reduction, improvement of injection technique, and additional treatment strategies. Referring to this, animal model showed increased efficacy and decreased systemic side effects of BoNT in the injected muscle after active or passive manipulation of muscle. The mechanism of this effect remain unclear.