Rotenone, an environmental toxin, is used to induce neurodegeneration in both the cellular and animal model of Parkinson's disease. Demethoxycurcumin (DMC), derivative of curcumin has been reported to have antioxidant and anti-inflammatory characteristics in in vitro and in vivo PD conditions. The present study was aimed to evaluate the efficacy of DMC in the management of neurodegeneration in PD. Male Wistar rats were radomized and divided into control, rotenone, DMC +rotenone and rotenone alone treated animals. Pre-treatment with DMC one hour prior to the rotenone injection, attenuated the motor and non-motor deficits. Western blot analysis indicated that the administration of DMC to PD rats eased the protein expression of dopaminergic and apoptotic indices. These findings showed that DMC effects on ameliorating the PD symptoms induced by rotenone might be associated with the neuroprotective and antioxidant effects of this compound.