This study was designed to assess the potential therapeutic efficacy of gene-modified mesenchymal stem cells (MSCs), MSCs-TH and MSCs-GDNF, in PD rats. Fifty-nine PD rat models were divided into five groups and then the gene-modified MSCs were transplanted into the striatum of rats according to the design. Apomorphine-induced rotational behavior in rats was observed weekly; rats which received both MSCs-TH and MSCs-GDNF showed the most significant improvement compared with those in other groups (P < 0.01). Three weeks later, immunohistochemistry analysis found TH-positive cells and GDNF-positive cells in striatal. Eight weeks later, PD rats were killed. HPLC and ELISA results showed DA and GDNF content in striatum of rats which received both MSCs-TH, and MSCs-GDNF was considerably higher compared with those of other groups (P < 0.01),respectively. In conclusion, our results suggest that combined transplantation of MSCs expressing TH and GDNF can lead to remarkable therapeutic effects in a rat model of PD.