Objective. To evaluate the efficacy of semax and timing of rehabilitation on the dynamics of plasma BDNF levels, motor performance, and Barthel index score in patients after ischemic stroke (IS). Material and methods. One hundred and ten patients after IS (43 men, 67 women, mean age 58.0±9.7, Ме 63 years) were examined. All patients were divided into early (89±9 days) and late (214±22 days) rehabilitation groups. Each group was subdivided into semax+ and semax− subgroups. Standard regimen of semax included 2 courses (6000 mcg/day) for 10 days with 20 day interval. Plasma BDNF levels, motor performance on the British Medical Research Council scale and Barthel index were assessed in all groups. Results. Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period. In semax− subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation. Conclusions. Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance.