Abstract: The development of more effective deep brain stimulation (DBS) paradigms for Parkinson’s disease is limited by the non-specific nature of electrical stimulation. Optogenetics, with its spatial and cell-type specificity, is a potential alternative therapeutic approach. In 6-hydroxydopamine-induced hemi-Parkinsonian rats, we investigated the therapeutic values of optogenetic modulation of the subthalamic nucleus (STN) and the motor cortex. Here we report optogenetic inhibition of principal neurons in the STN significantly improved hemi-Parkinsonian motor asymmetry, measured by amphetamine-induced rotations. We also show preliminary results that revealed therapeutic improvement in motor asymmetry by single-site optogenetic excitation of the motor cortex. Although improvement from optogenetic modulations did not exceed the effects of DBS in the STN, our findings suggest that spatially patterned optogenetic stimulation of the cortex, i.e., more precise manipulation of cortical activity over larger area, should be investigated as a therapeutic approach for Parkinson’s disease.