Introduction: Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNPC) is the principal cause of symptoms of PD. It has been suggested that ghrelin, a peptide transgenic arc, may play an important role in protecting neurons in SNPC. Furthermore, exercise improves the brain function and upregulates the expression of neurotrophic factor in the striatum. Nicotine affects different types of nicotinic receptors within the nigrostriatal-dopaminergic pathway. The aim of the present study was to evaluate the effect of ghrelin, exercise, and nicotine on catalepsy in reserpine-induced PD model in rats. Materials and Methods: 114 Wistar rats were divided into 19 groups. To induce PD model, reserpine (1mg/Kg; dissolved in glacial acetic acid solvent 0.03 ml) was injected intrapritoneally (i.p.)  and catalepsy was assessed by test bars. Rats in exercise group were forced to have treadmill exercise (5 days a week for 20 minutes at a speed of 24 meters per minute at zero slope). Ghrelin was injected (i.p., 0.1 mg/Kg) for 21 days and nicotine (i.p., 0.002 mg / kg) was injected for 21 days. Results: The catalepsy was significantly reduced in PD rats treated with ghrelin, exercise, and nicotine. Conclusion: A combined treatment with ghrelin, exercise, and nicotine could be a potential treatment for catalepsy in patient with PD.