Exercise exerts helpful effects in Parkinson's disease. In this study, the 6-hydroxydopamine (6-OHDA) injection was used to investigate the effect of exercise on apomorphine-induced rotation and neurorestoration. Rats (n = 32) were divided into four groups: (1) Saline+Noexercise (Sham); (2) 6-OHDA+Noexercise (6-OHDA); (3) Saline+Exercise (S+EXE), and (4) 6-OHDA+Exercise (6-OHDA+EXE). The rats were administered 8 μg 6-OHDA by injection into the right medial forebrain bundle. After 2 weeks, the exercise group was run (14 consecutive days, 30 min per day). One month after the surgery, following the injection of apomorphine, the 6-OHDA group displayed a significant increase in rotation and the 6-OHDA+EXE group showed a significant reduction of rotational asymmetry (P < 0.001). 6-OHDA injection reduced the mRNA and protein expression of the AMP-activated protein kinase, brain-derived neurotropic factor, and tyrosine hydroxylase in relation to the Sham group and exercise increased these levels. Expression of the silent information regulator 2 homolog 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha was unexpectedly enhanced in the 6-OHDA groups in relation to the Sham group. These findings suggest that the 6-OHDA injection increased the neurodegeneration and mitochondrial and behavioral dysfunctions and the treadmill running attenuated these disorders in the ipsilateral striatum of the 6-OHDA+EXE group.